Information

Rx

Prescribing

Good

Consumerism

and

Responsible

Citizenship

Recent

medical

informatics

and

sociological

literature

has

painted

the

image

of

a

new

type

of

patient

one

that

is

reflexive

and

informed

with

highly

specified

information

needs

and

perceptions

as

well

as

highly

developed

skills

and

tactics

for

acquiring

information

Patients

have

been

re-named

reflexive

consumers

At

the

same

time

literature

about

the

questionable

reliability

of

web-based

information

has

suggested

the

need

to

create

both

user

tools

that

have

pre-selected

information

and

special

guidelines

for

individuals

to

use

to

check

the

individual

characteristics

of

the

information

they

encounter

In

this

article

we

examine

suggestions

that

individuals

must

be

assisted

in

developing

skills

for

reflexive

consumerism

and

what

these

particular

skills

should

be

Using

two

types

of

data

-LRB-

discursive

data

from

websites

and

promotional

items

and

supplementary

data

from

interviews

and

ethnographic

observations

carried

out

with

those

working

to

sustain

these

initiatives

-RRB-

we

examine

how

users

are

directly

addressed

and

discussed

We

argue

that

these

initiatives

prescribe

skills

and

practices

that

extend

beyond

finding

and

assessing

information

on

the

internet

and

demonstrate

that

they

include

ideals

of

consumerism

and

citizenship

Introduction

In

discussions

about

the

increasing

use

of

internet

technologies

in

health

care

a

new

kind

of

patient

has

slowly

been

constructed

a

patient

that

is

reflexive

and

informed

with

highly

specified

information

needs

and

perceptions

as

well

as

highly

developed

skills

and

tactics

for

acquiring

information

This

specific

depiction

of

the

patient

transforms

the

patient

into

an

active

participant

in

his

or

her

care

empowered

through

training

skill

development

and

the

use

of

technologies

such

as

the

world

wide

web

all

of

which

can

be

provided

or

enabled

by

government

organizations

or

other

political

actors

Through

increased

access

to

medical

information

coming

from

outside

of

the

health

care

arena

the

boundary

between

lay

and

expert

is

breaking

down

enabling

patients

to

become

experts

be

more

assertive

in

managing

their

own

care

and

change

the

nature

of

their

existing

relationships

with

health

care

professionals

-LSB-

-RSB-

As

Henwood

et

al.

-LSB-

-RSB-

point

out

however

just

because

the

potential

for

empowerment

exists

it

does

not

necessarily

occur

Patients

conform

only

with

difficulty

to

the

images

associated

with

the

reflexive

consumer

and

the

concept

of

the

informed

patient

is

empirically

difficult

to

sustain

-LSB-

-RSB-

Becoming

informed

requires

skills

related

both

to

information

and

to

the

various

media

that

can

be

used

to

access

that

information

Patients

reflect

low-level

skills

with

respect

to

searching

for

information

rely

on

intermediaries

and

experience

concrete

barriers

during

the

medical

encounter

all

of

which

act

as

actual

constraints

on

the

emergence

of

informed

patients

-LSB-

-RSB-

In

literature

about

the

questionable

reliability

of

web-based

information

the

suggestion

that

lay

information

seekers

are

constrained

in

conforming

to

this

image

is

too

mild

This

body

of

literature

asserts

the

stronger

position

that

they

are

actually

prevented

from

being

empowered

because

of

the

large

amount

of

information

and

the

questionable

quality

of

much

of

that

information

Central

in

this

discussion

is

the

concern

that

even

if

patients

manage

to

find

web-based

medical

information

they

lack

the

skills

necessary

to

evaluate

the

quality

of

that

information

and

therefore

are

especially

vulnerable

to

harmful

information

in

the

form

of

errors

fraud

and

quackery

-LSB-

-RSB-

This

concern

is

answered

by

the

argument

that

a

pressing

need

exists

for

educating

patients

in

how

to

judge

a

website

's

reliability

-LSB-

-RSB-

Taken

together

these

discourses

construct

patients-as-web-users

that

are

simultaneously

skilled

and

capable

but

also

incompetent

and

unskilled

The

informed

patient

must

be

educated

in

how

to

search

for

and

assess

information

in

order

to

conform

to

the

definition

of

a

reflexive

empowered

consumer

Patients

are

not

empowered

merely

through

access

to

the

internet

or

web-based

information

-LSB-

-RSB-

but

this

literature

suggests

must

be

constructed

in

the

process

of

being

led

to

pre-selected

information

by

health

professionals

and

information

specialists

In

suggesting

the

need

to

create

user

tools

that

have

pre-selected

information

as

well

as

guidelines

for

patients

to

use

to

check

the

individual

characteristics

-LRB-

author

sources

date

underlying

financial

sponsorship

etc.

-RRB-

of

the

information

they

encounter

authors

emphasize

the

boundary

between

lay

and

expert

assessments

of

information

privileging

the

latter

over

the

former

Existing

literature

prescribes

that

patients

utilize

government-provided

medical/health

portals

click

on

hyperlinked

icons

-LRB-

seals

of

approval

or

trust

marks

-RRB-

provided

by

non-profit

or

non-governmental

organizations

follow

checklists

created

by

professionals

or

health

educators

and/or

download

special

toolbars

all

of

which

will

assist

them

in

finding

and

evaluating

information

on

the

web

Because

web

pages

provide

powerful

examples

of

pre-defining

-LRB-

or

pre-confining

-RRB-

how

information

technologies

should

work

how

they

should

be

perceived

and

how

different

actors

should

utilize

them

it

is

important

to

study

the

discourses

that

they

carry

-LSB-

-RSB-

However

little

attention

has

been

given

to

the

underlying

prescriptions

about

skills

and

use

as

well

as

additional

political

agendas

and

messages

about

individual

behavior

that

individual

web-based

reliability

initiatives

such

as

portals

seals

and

special

toolbars

convey

In

this

article

we

look

not

at

how

patients

assess

information

-LRB-

or

what

skills

they

do/not

reflect

-RRB-

but

rather

at

what

health

educators

medical

professionals

and

review

organizations

suggest

the

skills

of

a

reflexive

consumer

should

be

We

view

the

various

user

tools

such

as

guidelines

checklists

portals

and

clickable

seals

as

artifacts

with

politics

-LSB-

-RSB-

particularly

the

politics

of

building

consumer-citizens

and

shaping

their

skills

perceptions

and

behaviors

We

begin

by

looking

at

more

general

literature

about

the

construction

of

users

and

designers

followed

by

a

review

of

literature

that

transforms

potentially

informed

patients

into

reflexive

consumers

Using

two

types

of

data

front

page

data

-LRB-

information

images

quotes

gleaned

directly

from

websites

and

their

accompanying

promotional

items

-RRB-

and

supplementary

behind

the

scenes

data

from

interviews

and

observations

carried

out

with

those

working

to

sustain

given

initiatives

we

examine

how

users

are

directly

addressed

and

discussed

How

are

users

enrolled

by

sites

and

promotional

items

What

ideals

are

represented

in

these

user

tools

and

in

what

kind

of

practices

are

they

embedded

We

argue

that

although

these

examples

claim

to

target

all

citizens

the

prescriptions

for

action

that

these

user

tools

carry

suggest

that

the

user

envisioned

by

the

developers

of

these

tools

is

not

everybody

but

rather

a

specific

ideal

type

of

user

the

good

consumer

responsible

citizen

In

order

to

develop

skills

for

finding

and

assessing

information

on

the

internet

patients

must

engage

in

certain

practices

practices

that

also

enable

developing

the

skills

necessary

to

share

the

responsibility

for

information

reliability

and

to

be

an

empowered

health

consumer

and

responsible

citizen

The

Importance

of

the

State

in

Configuring

Users

of

Technologies

Studies

of

science

technology

and

society

-LRB-

STS

-RRB-

have

a

long

tradition

of

reflecting

on

how

users

are

or

are

not

included

in

the

design

and

implementation

of

different

technologies

Woolgar

-LSB-

-RSB-

argues

that

designer

preconceptions

about

use

can

shape

what

counts

as

legitimate

behavior

and

that

users

are

configured

i.e.

their

identity

and

skills

are

defined

and

constraints

upon

their

-LRB-

possible

future

-RRB-

actions

are

set

before

the

technologies

ever

reach

the

anticipated

user

group

Because

of

this

configuring

technologies

can

be

read

as

carrying

specific

scripts

for

use

-LSB-

-RSB-

Rose

and

Blume

-LSB-

-RSB-

however

have

criticized

much

of

the

subsequent

work

on

configuring

users

because

it

attributes

configuration

largely

to

market-driven

design

and

pays

too

little

attention

to

the

possibility

of

states

as

providers

or

enablers

of

technology

use

and

therefore

neglects

to

consider

the

potential

role

states

have

in

user

configuration

According

to

Rose

and

Blume

focusing

on

technologies

that

are

developed

or

facilitated

by

the

state

and

its

institutions

may

highlight

significant

tensions

between

individuals

as

users

and

the

state

of

which

they

are

members

and

citizens

Policy

documents

can

develop

meanings

for

information

technologies

by

providing

for

example

the

language

of

discourse

about

those

technologies

-LSB-

-RSB-

In

their

behavior

and

discourse

collective

providers

much

like

market-like

providers

presume

that

individuals

will

be

active

consumers

of

technologies

meaning

that

the

state

may

enact

policies

that

while

not

overtly

or

explicitly

configuring

the

user

do

create

or

maintain

an

environment

that

helps

to

shape

how

users

are

configured

In

using

certain

technologies

-LRB-

or

by

using

them

in

the

specified

ways

-RRB-

individuals

fit

with

their

configurations

and

follow

the

technologies

scripts

and

actualize

their

potential

as

good

citizens

-LSB-

-RSB-

Singleton

-LSB-

-RSB-

makes

a

similar

point

with

her

suggestion

that

the

New

Public

Health

in

the

UK

seeks

to

train

citizens

in

more

ways

than

one

She

asserts

that

training

programs

for

healthy

citizens

are

not

just

about

physical

health

but

also

about

practical

skills

and

about

distinguishing

between

active

and

inactive

citizens

Klecun-Dabrowska

and

Cornford

-LSB-

-RSB-

have

also

looked

at

the

recent

discourses

on

health

in

the

UK

specifically

focusing

on

the

role

of

telemedicine

within

wider

national

and

international

debates

on

health

They

too

saw

that

documents

convey

a

vision

of

a

refocused

health

care

system

to

serve

a

population

that

has

enough

information

resources

to

enable

individuals

to

manage

their

own

care

and

participating

more

actively

in

the

health

care

process

Information

they

argue

is

transformed

into

something

that

is

easily

captured

understood

and

transformed

to

achieve

wider

goals

goals

related

to

social

responsibility

and

community

values

At

the

same

time

states

want

to

forward

their

political

agendas

and

invent

new

modes

of

indirect

steering

for

empowering

their

members

such

that

they

freely

willingly

and

self-reflexively

choose

the

paths

toward

the

desired

outcomes

of

the

state

The

possibility

of

the

state

to

directly

influence

its

citizens

is

made

relative

as

the

state

competes

with

other

types

of

influences

This

has

led

to

the

development

of

new

types

of

steering

where

governments

seek

to

rule

the

social

indirectly

through

designing

facilitating

and

moderating

processes

of

self

and

co-governance

-LSB-

-RSB-

More

communicative

and

cooperative

modes

of

re-centering

allow

for

bottom

up

articulation

without

relinquishing

everything

to

citizen

preferences

Again

these

programs

are

not

just

about

the

empowerment

of

individuals

or

about

the

distribution

of

expertise

but

are

also

about

distinguishing

between

active

and

inactive

citizens

Although

states

demonstrate

a

readiness

to

engage

in

active

teamwork

and

argue

the

need

for

collaborative

solutions

Bang

argues

that

they

nonetheless

reveal

how

key

relationships

are

re-imagined

and

redrawn

Two

things

are

worthy

of

note

first

the

terms

re-imagining

and

redrawing

suggest

that

something

new

can

emerge

which

is

a

distinct

possibility

However

with

respect

to

the

internet

at

least

studies

have

shown

that

the

boundaries

that

are

constructed

around

information

for

example

tend

to

reinforce

existing

social

ideas

-LSB-

-RSB-

and

geographic

borders

-LSB-

-RSB-

The

lines

that

are

redrawn

serve

only

to

reinforce

what

is

already

there

Second

the

exclusive

focus

on

states

tends

to

neglect

the

role

of

other

political

actors

Especially

in

activities

regarding

reliable

medical

information

states

are

not

alone

but

are

joined

by

non-governmental

organizations

-LRB-

NGOs

-RRB-

and

inter-governmental

organizations

-LRB-

IGOs

-RRB-

as

well

as

non-profit

organizations

voicing

their

own

political

advocacy

agendas

We

extend

the

analysis

in

this

paper

to

look

at

both

programs

from

federal

agencies

and

initiatives

created

by

other

types

of

political

institutions

These

programs

and

initiatives

provide

tools

for

accessing

and

assessing

information

on

the

web

in

some

cases

enabling

information

provision

-LRB-

See

Textbox

for

an

overview

of

the

different

initiatives

that

are

used

as

examples

-RRB-

For

example

the

US

Department

of

Health

and

Human

Services

provides

a

portal

with

contact

information

for

organizations

-LRB-

-RRB-

and

the

US

National

Library

of

Medicine

-LRB-

NLM

-RRB-

provides

a

portal

with

health

content

from

the

National

Institutes

of

Health

-LRB-

-RRB-

Outside

of

the

US

the

Health

on

the

Net

Foundation

-LRB-

HON

-RRB-

in

Geneva

seeks

to

raise

awareness

about

ethical

issues

related

to

providing

medical

information

while

the

World

Health

Organization

-LRB-

WHO

-RRB-

proposes

the

creation

of

a

health

domain

afforded

only

to

sites

meeting

specific

criteria

of

home

pages

for

cited

examplesHealthfinder

is

the

official

Federal

Gateway

to

health

information

provided

by

the

US

Department

of

Health

and

Human

Services

is

a

portal

provided

by

the

US

National

Library

of

Medicine

seeks

to

combat

health

fraud

and

is

run

by

Dr.

Stephen

Barrett

on

the

Net

is

a

Geneva-based

non-governmental

organization

that

provides

diverse

user

tools

The

focus

of

this

study

is

the

principle

HON

Code

of

Conduct

and

accompanying

hyperlinked

seal

was

funded

by

the

EU

from

the

Action

Plan

on

promoting

safer

use

of

the

Internet

by

combating

illegal

and

harmful

content

on

global

networks

The

collaborative

MedCIRCLE

is

a

follow-up

that

provides

users

with

a

downloadable

toolbar

's

QMIC

is

a

three-tiered

trust

mark

for

medical

websites

in

the

Netherlands

The

third

tier

signifies

content

review

of

information

World

Health

Organization

recently

released

a

list

of

approved

sites

for

vaccine

safety

These

self-ascribed

roles

lead

to

numerous

questions

such

as

why

UN

NGO

status

-LRB-

in

the

case

of

HON

-RRB-

or

a

neutral

position

-LRB-

claimed

by

the

WHO

-RRB-

is

crucial

to

building

claims

about

the

reliability

of

medical

information

Why

is

a

gov

domain

more

reliable

than

a

com

and

where

does

the

org

domain

rank

in

relation

to

other

existing

and

proposed

domains

What

potential

tensions

arise

between

states

and

citizens

-LRB-

or

even

NGOs

and

citizens

-RRB-

in

these

settings

Although

these

questions

would

be

difficult

to

answer

they

do

give

us

cause

to

think

about

the

political

messages

that

are

sent

to

lay

information

seekers

when

they

are

instructed

on

how

to

search

for

evaluate

and

use

web-based

medical

information

Informed

Patients

Reflexive

Consumers

Ideal

Citizens

This

entire

line

of

discourse

about

empowering

patients

and

the

role

of

web-based

information

has

led

to

the

semantic

challenge

of

properly

naming

those

non-medically

trained

individuals

searching

for

information

online

For

example

the

term

patient

does

not

encapsulate

those

persons

who

search

for

information

regarding

the

health

situation

of

a

family

member

or

friend

Miller

and

Reents

-LSB-

-RSB-

alternative

information

retrievers

makes

the

user

too

passive

while

the

suggested

informatics

alternative

medical

end-users

-LSB-

-RSB-

makes

the

route

to

the

information

too

technology

specific

without

reflecting

the

social

aspects

of

information

use

and

broader

information

landscapes

-LSB-

-RSB-

that

persons

can

access

Furthermore

the

term

medical

does

not

reflect

broader

issues

related

to

health

and

fails

to

allow

for

use

of

information

by

those

that

Kivits

-LSB-

-RSB-

calls

healthy

internet

users

those

not

necessarily

afflicted

by

illness

but

nonetheless

interested

in

health

information

The

concepts

citizen

and

consumer

are

terms

for

users

that

are

used

most

often

by

those

creating

different

web-based

reliability

initiatives

working

under

the

suggestion

that

these

terms

are

neutral

and

avoid

the

semantic

problems

mentioned

above

-LSB-

see

for

example

-RSB-

However

these

words

also

carry

connotations

Anderson

et

al.

even

go

so

far

as

to

state

When

speaking

about

consumers

from

this

model

it

should

become

clear

that

we

mainly

refer

to

educated

patients

with

chronic

diseases

from

developed

countries

-LRB-

-RRB-

Using

these

two

terms

more

generally

implies

certain

rights

such

as

Gustafson

and

Wyatt

's

-LSB-

-RSB-

assertion

that

consumers

deserve

both

high

quality

content

and

a

certain

degree

of

confidence

in

the

information

they

use

but

such

use

also

connotes

certain

responsibilities

Each

of

the

initiatives

to

which

the

usage

of

these

terms

is

attached

defines

particular

types

of

participation

that

extend

beyond

gathering

information

to

include

activities

in

the

health

care

process

and

social

community

at

large

The

consequence

of

course

is

that

teaching

patients

how

to

search

for

and

assess

information

on

the

web

becomes

more

than

just

a

process

of

constructing

empowered

patients

it

extends

further

to

inscribe

notions

of

good

consumerism

and

responsible

citizenship

When

we

couple

the

discussion

about

empowerment

on

the

practical

skills

that

users

are

expected

to

develop

we

see

that

it

takes

place

within

an

overt

and

dominant

biomedical

discourse

-LSB-

-RSB-

which

is

framed

not

only

by

medical

professionals

but

also

by

political

actors

For

example

in

relation

to

assessing

web-based

health

information

Edgar

et

al.

-LSB-

-RSB-

describe

three

essential

skills

the

ability

to

conduct

a

search

and

find

the

right

sites

the

ability

to

judge

the

quality

of

information

found

on

a

given

site

and

the

ability

to

synthesize

that

information

into

a

useful

context

for

personal/individual

health

Eng

and

Gustafson

-LSB-

-RSB-

argue

however

that

the

skill

is

more

than

just

assessing

and

using

information

but

is

actually

about

deciding

which

of

the

existing

tools

works

best

for

the

individual

Only

in

finding

the

right

tool

can

s/he

implement

a

personal

evaluative

framework

and

learn

how

to

be

an

educated

consumer

How

the

Initiatives

Enroll

Citizens

and

Consumers

Each

of

the

initiatives

discussed

in

this

paper

attempts

to

enroll

internet

users

in

specific

activities

of

finding

and

assessing

health

information

The

most

prominent

strategy

of

enrollment

that

we

see

is

the

suggestion

of

abounding

risks

to

personal

health

and

the

simple

ways

to

combat

them

Involvement

learning

how

to

check

information

actively

and

always

becomes

a

matter

of

personal

responsibility

and

an

identifying

component

of

reflexive

information

consumption

Failure

to

learn

about

user

tools

and

use

them

as

prescribed

is

to

be

inactive

and

therefore

deviant

or

lacking

-LSB-

-RSB-

Highlighting

Risks

and

Providing

Simple

Instructions

for

Combating

Them

One

evident

strategy

for

interesting

patients

in

the

need

to

check

the

reliability

of

the

information

is

the

construction

of

web-based

information

as

information

that

puts

individuals

at

risk

Because

of

the

nature

of

the

web

information

can

come

from

anyone

anywhere

it

originates

outside

of

a

given

country

in

another

medical

tradition

or

health

care

context

and

as

such

it

is

foreign

and

worthy

of

suspicion

If

information

is

n't

pre-approved

individuals

could

be

making

their

decisions

based

on

wrong

information

fraud

or

quackery

An

individual

's

health

is

potentially

endangered

because

this

information

is

always

potentially

just

one

mouse-click

away

and

is

difficult

to

distinguish

from

truly

reliable

information

In

the

language

of

this

discourse

boundaries

are

constructed

around

information

these

boundaries

distinguish

for

example

between

geographic

locations

but

also

reinforce

more

traditional

ideas

by

distinguishing

between

lay

persons

and

experts

The

proposed

need

to

implement

user

education

programs

for

checking

the

reliability

of

the

information

they

encounter

suggests

that

anyone

online

should

be

aware

of

this

potential

for

harm

and

therefore

actively

involved

in

policing

that

information

-LSB-

-RSB-

HON

for

example

currently

includes

information

on

its

website

about

being

a

vigilant

user

Instructions

about

clicking

and

verifying

proper

use

of

its

HONcode

icon

is

prefaced

by

the

following

Unfortunately

we

can

not

banish

incompetence

or

fraud

from

the

medical

Internet

If

you

come

across

a

healthcare

Web

site

that

you

believe

is

either

possibly

or

blatantly

fraudulent

and

does

NOT

display

the

HONcode

please

alert

Quackwatch

Of

course

if

such

a

site

DOES

display

the

HONcode

alert

us

immediately

HON

can

not

prevent

dishonest

operators

from

simply

cutting

and

pasting

the

HONcode

seal

onto

their

Web

sites

in

a

bid

to

enhance

their

credibility

We

do

conduct

our

own

random

checks

on

subscribers

to

ensure

they

remain

compliant

with

the

HONcode

But

we

also

rely

heavily

on

vigilant

Web

surfers

to

alert

us

to

dubious

sites

and

they

do

There

are

three

quick

ways

users

can

check

whether

a

chosen

site

featuring

our

seal

is

a

bona

fide

HONcode

subscriber

HON

points

out

to

users

that

it

needs

its

users

to

help

police

information

on

the

internet

It

invites

them

to

join

in

a

partnership

with

two

types

of

authorities

the

first

being

itself

an

overarching

political

organization

and

the

second

being

participants

from

the

community

of

medical

professionals

Active

policing

on

the

part

of

the

user

is

made

extremely

simple

and

practically

effortless

checking

information

is

also

as

easy

as

a

single

mouse

click

-LRB-

merely

clicking

on

a

small

icon

-RRB-

or

just

running

through

a

short

checklist

Taking

a

few

seconds

can

prevent

all

users

from

encountering

bad

information

whereas

not

checking

could

subject

the

user

to

fraudulent

or

otherwise

harmful

information

With

its

clickable

trust

HON

provides

users

with

an

easy

tool

to

double

check

the

background

of

the

web

information

provider

This

type

of

tool

makes

the

action

of

checking

information

is

made

simple

and

non-time

consuming

as

easy

as

a

mouse

click

The

MedCERTAIN

project

which

proposed

a

mechanism

similar

to

HON

's

clickable

seal

except

that

it

proposed

to

include

content

review

in

addition

to

review

of

ethical

principles

produced

a

prototype

with

the

instruction

Remember

to

verify

by

simply

clicking

on

it

Similarly

the

Dutch

QMIC

trust

mark

states

In

the

blink

of

an

eye

you

can

see

that

information

is

reliable

and

correct

The

user

that

all

of

these

organizations

presuppose

is

someone

who

like

the

project

reviewers

is

-LRB-

or

should

be

-RRB-

familiar

with

the

ethical

issues

underlying

the

provision

of

any

but

especially

medical

information

on

the

web

We

begin

to

see

how

political

actors

invent

new

modes

of

indirect

steering

for

empowering

users

such

that

they

choose

specific

paths

They

attribute

to

these

users

skills

and

practices

more

in

keeping

with

professional

levels

of

information

assessment

and

action

But

they

also

make

these

practices

user

friendly

by

emphasizing

the

ease

with

which

information

can

be

checked

with

little

additional

thought

or

demands

on

time

and

by

encouraging

participation

in

partnerships

with

them

Directing

Paths

Toward

Information

The

various

initiatives

also

emphasize

their

links

to

the

medical

community

and

partnerships

with

one

another

This

is

evident

in

at

least

three

forms

logos

from

other

departments

and

organizations

placed

on

websites

joint

projects

with

physician

's

organizations

and

overt

statements

about

the

best

course

of

action

that

are

located

on

websites

At

the

time

of

writing

HON

's

website

includes

the

logos

of

the

University

Hospital

the

EU

the

city

of

Geneva

and

Sun

Microsystems

The

tag

lines

for

each

individual

logo

identify

how

these

different

groups

provide

social

and

technical

support

for

HON

and

its

web

activities

These

logos

show

that

HON

is

part

of

a

larger

national

and

international

community

that

transcends

medical

practice

politics

and

businesses

and

suggest

that

evaluating

medical

information

on

the

web

can

only

be

done

in

this

context

Some

studies

of

patient

searching

behaviors

have

indicated

that

patients

refer

to

their

physician

for

information

about

where

to

search

for

information

on

the

web

-LSB-

See

for

example

Cotton

and

Gupta

-RSB-

Recognizing

the

potential

of

taking

advantages

of

this

preference

for

physicians

as

trusted

sources

of

website

recommendations

but

also

recognizing

that

physicians

probably

do

not

have

time

to

review

scales

of

sites

some

initiatives

have

developed

-LRB-

or

furthered

existing

-RRB-

relationships

with

professionals

The

US

National

Library

of

Medicine

-LRB-

NLM

-RRB-

has

worked

with

professional

communities

to

develop

prescription

pads

for

web-based

information

-LRB-

see

Fig.

-RRB-

Fig.

of

one

version

of

the

prescription

pad

that

physicians

can

give

to

patients

during

the

consultation

to

refer

them

to

web-based

information

about

a

specific

health

topic

This

project

enabled

NLM

to

inform

physicians

about

the

topics

available

on

medlineplus

Additionally

it

supports

the

physician

and

patient

in

post-consultation

searches

for

health

information

With

this

information

prescription

the

physician

gives

the

patient

a

place

to

start

and

the

term

to

use

when

searching

on

the

web

for

information

specific

to

his

or

her

health

situation

and

that

starting

place

is

a

government

portal

In

this

trial

the

doctors

each

had

their

own

pre-printed

prescription

pad

The

prescription

pad

that

we

used

in

the

first

part

of

the

pilot

had

room

for

URLs

There

were

about

to

choose

from

and

they

chose

the

ones

that

they

saw

most

often

in

their

practices

What

we

found

is

that

the

doctors

do

n't

want

to

bother

with

all

that

They

want

to

have

their

own

prescription

pad

they

really

like

that

But

they

just

want

to

be

able

to

write

something

on

it

and

then

send

people

to

Medlineplus

Finally

websites

send

patients

back

and

forth

between

the

various

initiatives

and

tools

implicitly

and

explicitly

endorsing

one

another

HON

for

example

recommends

that

English-speaking

site

visitors

follow

a

specific

and

narrow

path

to

information

To

find

good

-LRB-

English-language

-RRB-

healthcare

information

you

can

bypass

the

all-purpose

commercial

search

engines

and

go

straight

to

healthcare

portals

like

Health

on

the

Net

-LRB-

-RRB-

or

Healthfinder

-LRB-

-RRB-

These

portals

have

already

eliminated

the

irrelevant

for

you

A

useful

rule

of

thumb

is

first

check

out

the

governmental

not-for-profit

and

hospital

Web

sites

or

those

carrying

an

immediately

recognizable

and

trusted

name

It

is

interesting

in

this

case

that

HON

excludes

more

commercial

search

engines

as

a

valid

route

to

information

The

message

is

that

web

tools

that

are

general

in

scope

rather

than

specifically

directed

toward

health

information

or

that

are

funded

by

commercial

interests

-LRB-

or

both

-RRB-

are

incorrect

choices

because

they

contain

too

much

extra

stuff

and

will

not

enable

the

user

to

find

what

s/he

is

looking

for

Reliability

is

redefined

as

an

issue

of

what

is

relevant

and

proper

behavior

involves

not

wasting

time

sifting

through

information

and

other

materials

that

are

according

to

HON

de

facto

irrelevant

Furthermore

in

emphasizing

that

HON

and

the

US

gateway

are

the

best

types

of

sites

HON

privileges

state

-LRB-

implicitly

working

with

medical

-RRB-

actors

over

other

types

of

actors

providing

medical

information

on

the

web

The

suggestion

then

is

that

engaging

in

good

searching

practices

and

finding/using

the

right

information

means

prioritizing

government

and

medical

channels

Through

these

statements

the

organizations

affirm

each

other

arguing

not

only

the

importance

of

a

joint

approach

to

reliability

but

also

the

importance

of

collaboration

between

different

countries

and

regions

The

risks

associated

with

misinformation

are

countered

with

initiatives

that

seek

to

rein

in

information

centralizing

it

at

certain

web

addresses

and

judging

it

according

to

politically

and

professionally

defined

criteria

One

example

would

be

the

criterion

for

levels

of

readability

-LSB-

-RSB-

applied

to

sites

such

as

Medlineplus

Another

would

be

the

use

of

selection

criteria

for

information

that

derive

from

similar

roots

-LSB-

-RSB-

or

the

transfer

of

existing

publishing

standards

to

evaluate

how

information

is

produced

-LSB-

-RSB-

Website

providers

enable

access

to

information

that

is

consolidated

and

repackaged

in

a

uniform

format

for

readability

and

then

placed

on

the

respective

site

under

a

uniform

design

and

structure

for

ease

of

navigation

Once

again

finding

and

using

good

information

is

made

easy

in

the

design

of

technology-specific

tools

What

is

interesting

are

the

personalized

messages

and

rhetoric

of

choice

in

which

these

standardized

formats

are

embedded

Healthfinder

is

your

guide

to

reliable

information

while

Medlineplus

provides

Trusted

health

information

for

you

Access

to

information

gives

users

new

choices

but

these

initiatives

convey

that

responsible

consumerism

and

reflexive

use

of

information

mean

choosing

narrow

routes

to

prepackaged

information

The

internet

offers

numerous

avenues

to

information

but

good

participation

means

utilizing

choice

to

choose

the

routes

provided

by

one

's

own

government

and

combining

these

with

overarching

non-governmental

organizations

or

other

non-profit

organizations

Individualizing

Choice

Along

the

Way

Both

HON

and

the

MedCIRCLE

initiative

have

taken

this

one

step

further

emphasizing

the

need

to

combine

top-down

control

of

information

with

bottom-up

user

choices

They

have

both

developed

special

toolbars

that

can

be

downloaded

and

coupled

on

the

user

's

internet

browser

-LRB-

see

Fig.

for

the

MedCIRCLE

prototype

-RRB-

Such

a

toolbar

allows

the

user

to

set

his/her

preferences

for

which

components

of

information

are

most

important

and

then

gives

a

confidence

rating

for

how

well

an

individual

website

answers

to

these

preferences

The

toolbar

gives

a

message

that

user

preferences

about

the

reliability

of

information

are

important

and

that

users

should

actively

set

their

own

criteria

for

assessment

However

this

is

acceptable

only

once

users

are

already

searching

within

the

confined

space

of

pre-approved

sites

Fig.

can

download

this

toolbar

from

and

set

their

own

preferences

for

characteristics

that

they

find

important

in

the

provision

of

health

information

The

confidence

rating

and

other

information

provided

by

the

tool

are

only

available

for

sites

already

in

the

HON

or

MedCIRCLE

databases

While

these

types

of

tools

suggest

the

importance

of

individual

choice

they

nonetheless

hold

individuals

responsible

for

following

the

right

paths

to

information

In

this

sense

the

discussion

is

not

merely

an

issue

of

creating

reflexive

consumers

but

also

of

judging

non-reflexivity

as

irresponsible

and

deviant

Following

the

Path

Back

to

the

State

The

responsibility

for

finding

good

information

and

avoiding

the

risks

associated

with

bad

information

on

the

internet

becomes

collaborative

and

distributed

Within

this

context

individuals

are

held

responsible

for

the

choices

they

make

how

they

engage

with

available

information

and

how

they

engage

with

other

actors

in

the

collaborative

process

This

process

involves

new

actors

such

as

HON

and

MedCERTAIN/MedCIRCLE

but

also

longer

standing

actors

such

as

the

WHO

state

governments

and

medical

associations

Reliability

is

created

through

distributing

skills

information

and

practices

and

is

intertwined

with

the

creation

of

new

networks

that

bind

together

the

technical

and

social

We

see

this

in

especially

in

uses

of

internet-based

technologies

to

further

public

health

education

Healthfinder

for

example

sends

monthly

newsletters

to

inform

its

public

about

changes

and

updates

to

the

site

and

about

different

services

it

provides

Each

newsletter

also

contains

a

list

of

health

observances

for

that

month

each

of

which

includes

hyperlinks

to

special

sites

with

more

information

These

observances

are

where

possible

coupled

on

the

-LRB-

national

-RRB-

holidays

being

celebrated

in

that

month

For

example

February

is

the

month

for

all

kinds

of

hearts

and

the

newsletter

's

healthy

observances

are

all

related

to

cardiac

issues

while

July

's

newsletter

focuses

on

food

safety

tips

for

warm

summer

days

and

firework

safety

tips

specifically

related

to

the

July

holiday

Although

other

months

are

more

general

all

months

prescribe

topics

of

suggested

interest

for

the

general

population

All

of

us

in

all

stages

of

life

can

find

a

health

observance

of

interest

this

month

April

's

observances

range

from

National

Donate

Life

Month

a

request

for

us

to

consider

giving

another

person

life

to

WalkAmerica

a

campaign

to

promote

the

benefits

of

carrying

babies

to

term

sponsored

by

March

of

Dimes

to

many

observances

in

between

The

observances

further

point

out

special

days

of

awareness

and

political

activism

and

also

broadly

publicize

public

health

education

opportunities

The

National

Headache

Foundation

is

sponsoring

National

Headache

Awareness

Week

June

to

recognize

headache

pain

as

a

real

and

legitimate

condition

and

encourage

those

who

suffer

with

headaches

to

see

a

physician

for

proper

diagnosis

and

treatment

This

year

's

campaign

Stop

Migraines

Before

They

Stop

You

will

feature

public

education

activities

nationwide

The

links

that

are

selected

for

inclusion

in

the

newsletters

link

largely

to

other

parts

of

the

Department

of

Health

and

Human

Services

and

to

other

health-related

government

institutions

-LRB-

gov

domain

endings

-RRB-

such

as

the

National

Institutes

of

Health

-LRB-

of

which

NLM

is

also

a

part

-RRB-

or

the

Centers

for

Disease

Control

and

Prevention

As

these

examples

show

different

actors

have

developed

practices

that

place

various

elements

in

new

and

unique

relationships

with

one

another

Issues

related

to

health

become

intertwined

with

for

example

federal

holidays

The

health

practices

of

the

individual

are

now

inextricably

linked

with

diverse

forms

of

community

participation

In

this

sense

health

education

and

enrollment

is

no

longer

only

or

primarily

about

verifying

online

health

information

but

rather

about

diverse

activities

that

extend

beyond

the

online

realm

Directly

Linking

Health

Practices

and

Citizenship

These

initiatives

are

tools

to

help

people

find

and/or

check

information

and

about

helping

lay

persons

become

empowered

not

merely

through

distribution

of

information

but

also

through

coaching

or

education

in

how

to

participate

more

actively

in

the

search

for

and

use

of

information

Users

are

invited

to

join

specific

defined

communities

that

will

in

one

way

or

the

other

protect

them

from

misinformation

and

inform

them

about

better

ways

to

act

HON

even

emphasizes

the

strength

and

necessity

of

its

partnership

with

lay

users

in

able

do

what

it

sets

out

to

do

HON

can

not

help

lay

users

if

the

lay

users

do

not

help

HON.

Additionally

there

is

a

normative

message

about

responsible

citizenship

HON

for

example

responds

to

individuals

who

follow

their

instructions

and

report

-LRB-

suspected

-RRB-

misuse

of

the

HONcode

icon

by

thanking

them

for

their

sense

of

civic

duty

and

healthfinder

's

newsletters

make

the

initiative

much

more

than

just

a

gateway

or

portal

to

links

of

organizations

with

information

They

also

serve

a

promotional

function

to

keep

visitors

returning

to

the

healthfinder

website

and

getting

them

to

link

through

to

other

government

sites

Further

still

they

show

that

being

an

active

consumer

and

responsible

citizen

involves

more

than

merely

checking

the

information

one

encounters

on

sites

or

reporting

misinformation

and/or

misuse

of

seals

through

certain

channels

The

responsibility

extends

into

all

areas

of

daily

life

-LRB-

from

good

nutrition

to

awareness

about

possible

diseases

-RRB-

and

extends

beyond

individuals

to

include

not

only

family

or

friends

but

also

the

community-based

or

social

responsibility

that

accompanies

participation

in

educative

programs

activism

or

fund-raising

events

What

begins

as

a

prescription

for

how

to

search

for

and

assess

information

on

the

web

actually

extends

to

the

entire

lifestyle

in

which

these

searching

activities

are

contextualized

-LRB-

As

Dessauer

-LSB-

-RSB-

notes

much

of

what

we

think

of

with

cyberspace

loses

meaning

and

referents

if

it

excludes

the

external

context

-RRB-

Interestingly

despite

the

varied

forms

of

the

messages

emanating

from

the

different

initiatives

each

of

the

prescribed

behaviors

such

as

entering

the

web

at

a

location

of

geographical

significance

-LRB-

within

government

borders

-RRB-

participating

in

a

chain

that

actively

polices

adherence

to

an

ethical

code

and

reports

misuse

or

even

downloading

and

using

a

browser

with

a

special

toolbar

emerges

as

simultaneously

optional

and

obligatory

-LSB-

-RSB-

Herein

lie

strains

of

the

tensions

that

are

suggested

by

both

Rose

and

Blume

and

Singleton

initiatives

are

created

and

promoted

under

the

guise

of

increasing

choice

and

democratization

but

the

actual

prescriptions

that

they

carry

entail

more

powerful

suggestions

about

which

choices

-LRB-

both

online

and

off

-RRB-

are

the

right

or

better

choices

with

alternatives

to

those

choices

being

-LRB-

explicitly

or

implicitly

-RRB-

discouraged

Discussion

In

this

paper

we

discuss

how

political

actors

have

enabled

access

to

web-based

information

largely

in

terms

of

specific

user

tools

however

through

these

examples

we

see

that

as

Markham

-LSB-

-RSB-

argues

access

to

the

internet

is

access

not

just

to

a

tool

but

to

a

place

-LRB-

emergent

in

for

example

how

the

interface

is

designed

or

the

level

of

engagement

in

a

given

activity

-RRB-

and

a

way

of

being

-LRB-

dependent

on

the

degree

to

which

the

individual

integrates

the

technology

into

his

or

her

understanding

of

social

construction

-RRB-

As

providers

or

enablers

of

technology

use

political

actors

at

various

levels

-LRB-

primarily

states

but

also

NGOs

and

IGOs

that

provide

different

types

of

sites

and

tools

-RRB-

provide

points

of

entry

and

create

avenues

not

just

to

online

information

but

to

online

and

offline

social

communities

with

specific

rules

for

behaviour

This

has

implications

for

how

technology

is

configured

within

the

relationship

between

individuals

and

the

state

and

other

political

actors

Especially

important

is

that

it

highlights

how

the

emphasis

on

claims

of

neutrality

within

the

reliability

debate

is

misplaced

Organizations

such

as

HON

or

WHO

who

claim

their

neutrality

based

on

their

international

scope

and/or

their

position

outside

of

national

governments

nonetheless

carry

specific

normative

ideas

of

acceptable

politically

or

socially

related

user

behavior

Likewise

individual

state

governments

that

claim

to

represent

the

needs

of

their

own

general

public

impose

values

on

the

information

that

they

recommend

to

that

public

for

example

in

privileging

a

gov

above

all

else

followed

by

a

org

or

edu

and

reducing

as

much

as

possible

endorsement

of

a

com

Existing

literature

arguing

the

need

for

collective

solutions

to

reliability

problems

together

with

the

abundant

presence

of

initiatives

offering

different

options

for

interactions

between

lay

end

users

and

those

providing

assessment

tools

indicate

a

readiness

among

political

actors

and

some

health

professionals

to

engage

in

active

teamwork

with

the

public

There

is

even

the

possibility

that

this

language

of

collaborative

efforts

suggests

that

the

public

is/can

be

seen

as

just

another

interest

group

balanced

with

physicians

-LSB-

-RSB-

However

in

the

examples

provided

above

we

see

that

partnership

does

not

necessarily

imply

equal

footing

for

each

of

the

three

types

of

actors

Organizations

use

the

catch-word

reliability

as

a

rhetorical

device

to

capture

attention

and

enroll

users

redirecting

their

information-seeking

behaviors

but

also

emphasizing

deeper-rooted

values

that

situate

individual

health-related

practices

within

a

greater

context

of

idealized

citizenship

As

such

in

addition

to

prescriptions

for

use

of

specific

tools

we

find

underlying

prescriptions

for

practices

that

reflect

good

citizenship

What

then

comprises

the

construction

of

a

good

citizen

First

and

foremost

a

good

citizen

is

one

who

is

interested

in

a

healthy

lifestyle

and

reflects

this

through

choosing

to

participate

in

activities

such

as

searching

for

information

about

his/her

health

and

the

health

of

loved

ones

Secondly

in

searching

for

this

information

the

citizen

reflects

the

possession

of

basic

practical

skills

by

choosing

to

align

his/her

practices

with

political

actors

thereby

choosing

for

sites

that

have

been

created

or

in

some

way

reviewed

by

these

actors

Thirdly

the

citizen

actively

participates

in

the

online

community

in

which

these

sites

are

embedded

Active

participation

includes

helping

to

police

the

information

online

by

checking

links

and

actively

reporting

misuse

Additionally

active

participation

includes

extending

knowledge

accrued

online

to

participate

in

offline

community

activities

-LRB-

activism

education

and

fund-raising

-RRB-

This

participation

also

forms

a

reciprocal

relationship

between

the

participant

and

the

given

organization

in

return

for

making

oneself

available

to

the

community

the

burden

to

search

for

find

and

evaluate

information

is

made

easier

Searching

can

be

done

using

tools

within

which

information

has

been

pre-selected

and/or

information

can

even

be

sent

directly

to

the

individual

's

personal

e-mail

Both

of

these

technical

options

for

acquiring

information

also

carry

an

implicit

social

promise

of

being

taken

care

of

protection

from

misinformation

or

mis-action

due

to

lack

of

information

The

readiness

to

participate

in

this

partnership

the

commitment

of

the

organization

to

helping

protect

its

user

community

is

made

explicit

Through

the

creation

of

initiatives

that

respond

to

debates

about

the

reality

of

information

online

organizations

prescribe

both

online

and

offline

behaviors

such

that

these

are

inextricably

intertwined

This

leads

to

the

emergence

of

new

collectives

counteracting

the

idea

that

internet

enables

people

to

separate

activities

with

ease

compartmentalizing

on

and

offline

activities

and

leading

to

division

These

collectives

further

counteract

notions

of

individualization

and

separation

from

the

community

as

well

as

arguments

that

certain

actors

can

be

rendered

irrelevant

Existing

relationships

become

re-conceived

as

new

alliances

between

medical

and

political

actors

where

internet

technologies

can

be

used

to

strengthen

existing

public

education

activities

Additionally

new

-LRB-

types

of

-RRB-

communities

emerge

families

and

friends

or

geographically

concentrated

communities

are

supplemented

by

communities

that

share

aspects

of

visiting

the

same

web

sites

and

participating

in

the

same

self-policing

chains

online

and

offline

individuals

participate

in

communities

by

watching

out

for

one

another

and

sharing

in

the

same

activities

Although

these

initiatives

claim

to

target

all

users

everywhere

they

actually

idealize

use

such

that

discussions

about

increased

choice

-LRB-

and

how

this

leads

to

patient

empowerment

-RRB-

also

carry

the

normative

implications

that

true

empowerment

is

only

possible

when

the

right

choices

are

made

Within

these

discussions

individuals

have

the

responsibility

to

develop

skills

that

make

them

informed

consumers

and

the

process

of

acquiring

these

skills

also

enables

them

to

contribute

their

part

to

the

greater

civic

communities

in

which

they

engage

The

additional

implications

connoted

by

the

terms

citizen

and

consumer

raise

the

question

of

whether

these

really

are

more

suitable

as

replacements

for

the

word

patient

than

other

suggested

alternatives

Conclusion

Whereas

discussions

of

technologies

and

their

users

have

largely

neglected

to

consider

the

role

of

states

-LRB-

and

other

political

actors

-RRB-

discussions

of

the

relations

of

states

and

individuals

have

not

always

considered

the

important

reciprocal

effects

of

and

on

changing

technologies

Discussions

of

skill

manage

to

link

individuals

to

individual

technologies

but

they

have

not

successfully

coupled

this

back

on

the

role

of

states

This

paper

has

used

the

discussion

about

the

reliability

of

web-based

information

to

attempt

to

bridge

these

gaps

and

demonstrate

the

integral

relationship

between

technologies

and

users

states

and

individuals

and

individuals

and

the

development

of

skills

It

shows

that

political

actors

including

both

governmental

and

non-governmental

organizations

make

presumptions

about

citizen

willingness

to

use

certain

technologies

and

as

such

utilize

soft

power

to

encourage

these

citizens-as-users-of-technologies

to

forward

certain

agendas

Under

the

guise

of

democratizing

ideals

and

suggestions

of

empowerment

they

use

policy

programs

and

web-based

tools

to

encourage

citizen

participation

Underlying

these

different

modes

of

participation

these

actors

are

able

to

re-create

boundaries

both

online

and

off

not

only

by

demarcating

geographical

boundaries

on

the

web

but

also

by

supporting

conventional

understandings

of

social

norms

such

as

the

role

of

the

medical

expert

as

a

primary

leader

In

so

doing

they

give

patients

the

choices

about

how

to

behave

with

strong

normative

undertones

about

rights

and

responsibilities

associated

with

being

informed

and

reflexive

consumers

As

others

have

pointed

out

where

medical

or

health-related

information

is

discussed

an

issue

of

power

is

usually

at

stake

-LSB-

-RSB-

The

power

in

question

is

generally

interpreted

as

that

of

medical

professionals

but

this

is

not

necessarily

the

only

interpretation

as

political

actors

clearly

use

this

for

their

own

means

and

ends

as

well

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

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reflexive consumerism
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Editorial to Echocardiographic assessment of left atrial ejection force and kinetic energy in chronic congestive heart failure It is well known , that the left atrium plays an important role in filling of the left ventricle : In first instance by being a reservoir of expansion during systole , than by being a conduit phase during diastole and finally by an active phase -LRB- if sinus rhythm is present -RRB- during late diastole -LSB- 1 -RSB- . This active phase has an important role in compensation of decreased left ventricular compliance in patients with heart failure . It is well known , that cardiac output decreases with 15 -- 20 % in patients who are in atrial fibrillation or are only paced in the ventricle -LSB- 2 -RSB- . This is not only of importance from pathophysiological point of view , but left atrial function is also an independent determinant of prognosis in patients with heart failure -LSB- 3 -RSB- . Stretch of the left atrium is generally controlled by intra-atrial pressure . The Frank -- Starling mechanism of the left atrium can be described by a biphasic increase of contraction force after increase of the stretch level . Left atrial function has been investigated with echocardiography for a long time -LSB- 4 -RSB- . One can make simple measurements of left atrial size or left atrial volume but also try to quantify left atrial function with Doppler and tissue Doppler . During heart failure , atrial function is characterised by augmented reservoir and pump function . This can be measured with pulsed wave Doppler across the mitral valve , which is generally expressed by a decreased E/A ratio . However , there is a marked heterogeneity among heart failure patients with pseudo normal patterns and restrictive filling patterns . This makes it difficult to use pulsed wave Doppler as a determinant of prognosis and guide therapy . The current paper of Tripokiadis et al. -LSB- 5 -RSB- , describes the measurement of left atrial ejection volume and left atrial ejection force in patients with heart failure . The method is not new and has been described in normal volunteers and patients with atrial fibrillation -LSB- 6 -RSB- . Although there were some limitations of the study in sample size , matching of age groups and gender , the authors were able to demonstrate , that left atrial function increases during heart failure and so compensated the decrease of left ventricular function . The model , described by Tripokiadis et al. can be used to estimate atrial function in patients with systolic and diastolic left ventricular dysfunction but also to evaluate the influence of atrial contribution to ventricular filling after medical treatment . Doing so , individual treatment can be optimised not only taking into account the clinical status , renal status , ventricular remodelling and neurohormonal status -LRB- BNP -RRB- , but also atrial contribution to left ventricular filling .

O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

left atrial function
heart failure
echocardiography


Murine neutrophils present Class II restricted antigen Neutrophils were originally described as short lived , terminally differentiated phagocytes that contribute only to the innate immune response . Recent evidence of neutrophil cytokine production and expression of numerous cell surface proteins has suggested that neutrophils are likely to influence adaptive responses and may satisfy the criteria of antigen presenting cells . Under certain inflammatory conditions human neutrophils express major histocompatibilty complex -LRB- MHC -RRB- Class II and the costimulatory molecules CD80 and CD86 . We have employed a murine T cell hybridoma with a transgenic T cell receptor specific for ovalbumin peptide 323 -- 339 -LRB- OVA323 -- 339 -RRB- , and a green fluorescent reporter of T cell receptor ligation , to directly investigate neutrophil-T cell interactions . These cells provide an ideal model system , allowing precise identification of antigen specificity and a clear readout of T cell activation . Additionally , whilst murine neutrophils have previously been shown to stimulate MHC Class I-dependent CD8 + T cell activation , CD4 + T cells stimulation via MHC Class II-expressing neutrophils has not been investigated . We addressed this by isolating murine neutrophils , loading with OVA323 -- 339 and co-culturing with T cells specific for the OVA323 -- 339/MHC Class II complex , and this resulted in T cell activation , as determined by expression of the green-fluorescent protein reporter . Antigen-pulsed neutrophils were also able to prime naïve OVA-specific CD4 + T cells in a contact-dependent manner , as shown by proliferation and cytokine production . Activation of lymphocytes was not due to contaminating macrophages . These studies demonstrate that murine neutrophils present MHC Class II-restricted peptides and induce T cell proliferation , confirming findings in human neutrophils , and demonstrate a novel pro inflammatory effect of murine neutrophils . 1 Introduction The range of functions ascribed to neutrophils has expanded significantly , from terminally differentiated , short-lived phagocytes that are solely involved in innate immune responses to cells that are now believed to influence the development of adaptive immune responses . Emerging evidence indicates that neutrophils may communicate with T cells through direct cell contact via major histocompatibility complex -LRB- MHC -RRB- Class I , Class II -LSB- 1,2 -RSB- , and co-stimulatory molecules -LSB- 3,4 -RSB- . Additionally , a neutrophil-derived cytokine milieu -LSB- 5 -RSB- may have significant impact on the adaptive response to infection , for example via neutrophil-derived IL-12 -LSB- 6,7 -RSB- . There is considerable evidence to suggest that neutrophils satisfy the criteria of antigen presenting cells , with some capacity to process antigen . Human neutrophils express MHC Class II , either following in vitro activation via CD11b -LSB- 8,9 -RSB- , with IFNγ , and GM-CSF -LSB- 10,11 -RSB- or following in vivo activation in RA synovial fluid -LSB- 4,12 -RSB- , in patients with active Wegener 's Granulomatosis -LSB- 13 -RSB- , in patients receiving GM-CSF -LSB- 14 -RSB- , and in persistent localized Staphylococcus aureus infections -LSB- 15 -RSB- . In addition to MHC Class II expression , stimulation of normal human PMN with IFNγ , or via CD11b induces CD80 and CD86 expression -LSB- 8,11 -RSB- . Human neutrophil presentation of superantigens is documented -LSB- 2 -RSB- . However , there are conflicting reports of neutrophils ' capacity to process and present tetanus toxoid on MHC Class II and activate T cells -LSB- 1,2 -RSB- . A capacity for extracellular antigen processing had been suggested as neutrophil gelatinase may cleave collagen to a Class II restricted immunodominant epitope -LSB- 16 -RSB- . Harding et al. demonstrated murine neutrophil Class I restricted antigen presentation -LSB- 17 -RSB- and additionally show that neutrophils processed phagocytosed bacteria via an alternate MHC Class I antigen-processing pathway , and such neutrophils may ` regurgitate ' processed peptide into the extracellular space and this peptide may then bind MHC Class I on neighbouring cells -LRB- e.g. macrophages -RRB- for presentation to CD8 cells -LSB- 17 -RSB- . Human studies of antigen-specific neutrophil-T cell interactions are confounded by low frequency of antigen-specific T cells in peripheral blood , variation of MHC allele expression , which therefore impedes ideal peptide antigen identification . To overcome these complications , we have employed a murine model system . Moreover , despite the important role of the neutrophil in the pathogenesis of numerous inflammatory diseases , many of which are modelled in rodents , there is a relative paucity of information on murine Class II restricted antigen presentation . We , therefore , sought to investigate whether murine neutrophils present antigens via MHC Class II . 2 Materials and methods 2.1 Murine peritoneal neutrophil and macrophage separation Peritoneal exudate cells -LRB- PEC -RRB- were obtained as previously described -LSB- 18 -RSB- . Briefly , 6 -- 8-week-old BALB/c mice -LRB- Harlan Olac , Bicester , UK -RRB- received 1.5 ml i.p. Brewers thioglycollate medium -LRB- Difco , East Molesey , UK -RRB- and 4 h later animals were sacrificed and cells harvested by peritoneal lavage . PEC were washed once then resuspended in 8 ml PBS , and layered over 3 ml Histopaque ® 1083 -LRB- Sigma , Poole , UK -RRB- , then centrifuged at 700 × g for 30 min at 20 °C . The enriched population of neutrophils contained within the cell pellet was washed twice in RPMI -LRB- Invitrogen , Paisley , UK -RRB- then resuspended at 2 × 106 ml − 1 in medium supplemented with 2 mM l-glutamine , 100 IU penicillin , 100 μg/ml streptomycin -LRB- all Invitrogen -RRB- and 10 % foetal calf serum -LRB- Harlan -RRB- . Peritoneal macrophages were obtained by adhering PEC to a polystyrene flask for 3 -- 4 h after which remaining adherent cells were incubated with ice cold PBS -LRB- without calcium or magnesium -RRB- at 4 °C for 10 min . Cells were harvested with a cell scraper , then washed in RPMI and resuspended at 2 × 106 ml − 1 . 2.2 Murine lymph node preparation DO11 .10 mice , with CD4 + T cells specific for the OVA323 -- 339 peptide in the context of the MHC Class II molecule I-Ad -LSB- 19 -RSB- were obtained originally from N. Lycke , University of Göteborg , Sweden . This T cell receptor is recognized by the KJ1 .26 clonotypic antibody . Single cell suspensions of lymph nodes from DO11 .10 mice were obtained by passing tissues through 100 μm Nitex membrane -LRB- Cadish , London , UK -RRB- using a 5 ml syringe plunger . To enrich for lymphocytes in lymph node cell suspensions , cells were resuspended at 4 × 106 ml − 1 in complete RPMI , and cultured in 150 cm3 polystyrene flasks -LRB- Iwaki , Japan -RRB- , for 2 h after which non-adherent cells were removed . Cells were washed three times in RPMI and resuspended at the desired cell concentration in complete RPMI with 25 mM HEPES . 2.3 Assessment of cell proliferation and cytokine production Cells were cultured under conditions indicated in figure legends . Where indicated , transwells -LRB- 0.2 μm membrane , Fisher Scientific , UK -RRB- separated cell populations . Cell proliferation was assessed by incorporation of -LSB- 3H -RSB- thymidine -LRB- 0.5 μCi/well -RRB- for the last 18 h of culture . Cells were harvested using a Betaplate 96-well harvester -LRB- Wallac Oy , Turku , Finland -RRB- and -LSB- 3H -RSB- thymidine incorporation measured on a Betaplate liquid scintillation counter -LRB- Wallac -RRB- . Concentration of cytokines in supernatants were estimated by ELISA . Paired antibodies -LRB- Pharmingen , Oxford , UK -RRB- were used in accordance with the manufacturer 's recommendations . All assays were optimised and validated prior to use . Maxisorp 96-well plates -LRB- Nunc -RRB- were coated with capture antibody in 0.1 M NaHCO3 overnight at 4 °C . Plates were blocked for 2 h ; samples and standards added for 2 h , followed by biotinylated secondary antibody for 1 h , then ExtrAvidin peroxidase -LRB- Sigma -RRB- conjugate for 45 min . Plates were developed with TMB -LRB- 3,3 ′ ,5,5 ′ - tetra-methylbenzidine , KPL , Gaithersburg , USA -RRB- , and then read at 630 nm with a Dynex MRX II plate reader and analysed using Dynex Revelation 3.2 software -LRB- Dynex , Middlesex , UK -RRB- . The levels of cytokine in supernatants were calculated by comparison with recombinant cytokine standards -LRB- R&D Systems , Abingdon , UK -RRB- . 2.4 Hybridoma cells The DO11.10-GFP hybridoma -LRB- kind gift of David Underhill , Department of Immunology , University of Washington , Seattle , Washington -LSB- 20 -RSB- -RRB- cells were grown in medium containing a 0.5 mg/ml geneticin . Co-cultures were established in which neutrophils or macrophages were incubated with 10 μg/ml OVA323 -- 339 peptide and DO11.10-GFP hybridoma cells , in the ratio indicated in the figure legends . Cells were cultured for 14 h , washed , and then analysed by flow cytometry . 2.5 Flow cytometry Aliquots of 1 × 106 cells in 12 mm × 75 mm polystyrene tubes -LRB- Falcon BD , Oxford , UK -RRB- were resuspended in 100 μl FACS buffer -LRB- PBS , 2 % FCS and 0.05 % NaN3 -RRB- containing Fc Block -LRB- Becton Dickenson , Oxford , UK -RRB- as well as appropriate antibody or isotype control . Neutrophils were identified with anti GR-1 -LRB- RB6-8C5 , Caltag -RRB- , macrophages with anti F4/80 -LRB- C1 : A3-1 , Caltag -RRB- , and MHC Class II assessed -LRB- 2G9 , BD Biosciences -RRB- , and T cells identified using anti CD4 + -LRB- RM4-5 , BD -RRB- and a clonotypic antibody specific for the OVA323 -- 339 TCR -LRB- KJ1 .26 -RRB- . After washing , samples were analyzed using a FACSCalibur flow cytometer equipped with a 488 nm argon laser and a 635 nm red diode laser and analyzed using CellQuest software -LRB- both BD -RRB- . 2.6 Statistical analysis Statistical analysis was performed on data as indicated in the figure legends , using Minitab software . 3 Results 3.1 Purification of murine neutrophils Neutrophils were purified from thioglycollate-induced peritoneal exudate cells -LRB- PEC -RRB- , as there is a relative paucity of neutrophils in murine peripheral blood -LRB- data not shown -RRB- . PEC were harvested 4 h post-thioglycollate administration , previously shown to be the peak of neutrophil recruitment , and after which an increasing proportion of macrophages are recruited -LSB- 18 -RSB- . Approximately 65 % of thioglycollate-induced PEC were identified as neutrophils on the basis of GR1 staining -LRB- data not shown -RRB- . PEC were further enhanced for neutrophils with a Ficoll gradient purification as previously described -LSB- 18 -RSB- . Following purification , samples were routinely 85 % GR1 positive -LRB- Fig. 1a -RRB- . Importantly , samples contained few macrophages -LRB- < 4 % -RRB- as determined by F4/80 staining -LRB- Fig. 1b -RRB- . Cytospins of neutrophil preparations were prepared and demonstrated characteristic multilobed nuclei in > 85 % or cells -LRB- data not shown -RRB- . Macrophage samples were 50 -- 60 % F4/80 positive cells -LRB- data not shown -RRB- . Murine neutrophils , expressing GR-1 , were found to express MHC Class II -LRB- Fig. 1c -RRB- , albeit at low levels relative to F4/80 positive macrophages -LRB- Fig. 1d -RRB- . 3.2 Murine neutrophils are able to present peptide antigen The murine T cell hybridoma , DO11.10-GFP , is activated by OVA323 -- 339 peptide in the context of I-Ad , without any requirement for co-stimulation . The hybridoma does not respond to peptide alone -LRB- Fig. 2 , ` background ' -RRB- . Neutrophils or macrophages alone had no effect on GFP expression by DO11.10-GFP . However , neutrophils or macrophages loaded with OVA323 -- 339 stimulated significant GFP expression by hybridoma cells when cultured at a 1:1 ratio . A dilution of macrophages was performed to estimate the contribution of contaminating macrophages to the results observed with neutrophil populations , demonstrating that at a ratio of 1 macrophage to 10 DO11.10-GFP cells , there was significantly less expression of GFP protein compared to that induced by neutrophils at a 1:1 ratio -LRB- Fig. 2 -RRB- . At a ratio of 1:100 , there was no consistent GFP expression detected -LRB- data not shown -RRB- . As there were < 5 % F4/80 positive macrophages contaminating the neutrophil samples , these titration experiments indicated that only a small proportion of the T cell hybridoma activation observed in the ` neutrophil presentation ' assays could be attributable to macrophage contamination . 3.3 Neutrophils can drive naïve T cell proliferation and cytokine production To investigate neutrophils antigen presentation in a co-stimulation dependent system , and the ability of neutrophils not only to present but also to prime T cells , neutrophils were co-cultured with primary T cells . Lymph nodes were obtained from DO11 .10 transgenic BALB/c mice . Single cell suspensions of lymph nodes were allowed to adhere to plastic for 3 h to remove the majority of adherent antigen presenting cells , after which the population was routinely 70 % CD3 positive -LRB- data not shown -RRB- . The presence of remaining endogenous APCs in the lymph node facilitated a strong response to OVA323 -- 339 peptide alone -LRB- Fig. 3a , c and e -RRB- . Therefore , neutrophils and macrophages were pulsed with OVA323 -- 339 for 2 h then washed three times to remove unbound peptide prior to the addition of transgenic T cells . Cells were co-cultured for 72 h at the ratios indicated in the figure legends . Neutrophils pulsed with OVA323 -- 339-induced proliferation -LRB- Fig. 3b -RRB- , IL-2 -LRB- Fig. 3d -RRB- and IFNγ -LRB- Fig. 3f -RRB- production . Low levels of IL-5 were detected in some experiments -LRB- data not shown -RRB- . The neutrophil-induced responses were less than those evoked by macrophages at the same cell ratio . A titration of macrophages was performed to give an estimate of the contribution of contaminating cells , demonstrating that only a small proportion of neutrophil-induced T cell responses could be attributable to contaminating macrophages . 3.4 Cell contact dependence of neutrophil T cell interactions To determine the relative contribution of cell contact dependent mechanisms and soluble factors in neutrophil-T cell interactions , cells were separated by 0.2 μm membranes placed between the cell populations , allowing diffusion of soluble proteins but preventing cell contact . The responding OVA323 -- 339-specific T cells were not a 100 % pure T cell population and contained some APCs , demonstrated by the lymph node response to OVA323 -- 339 alone -LRB- Fig. 4a and b ` OVA ' -RRB- . Thus , the transwells permitted investigation of whether lymph node-derived APCs were presenting soluble proteins derived from dead or degraded neutrophils . Bone marrow-derived dendritic cells -LRB- DC -RRB- were used as a positive control . Free OVA323 -- 339 or ConA crossed the transwell membrane and stimulated cell proliferation and cytokine production -LRB- Fig. 4a -RRB- . However , when antigen pulsed neutrophils were separated from the lymph node cells by the transwell , antigen-specific proliferation and cytokine production was reduced -LRB- Fig. 4a and b -RRB- . Importantly , antigen pulsed cell cultures did not release sufficient free antigen to stimulate a response from the OVA323 -- 339-specific T cells below -LRB- Fig. 4a -RRB- . Thus , the antigen-specific T cell proliferation and cytokine production induced by neutrophil antigen presentation is cell contact dependent . 4 Discussion Data presented here demonstrate that murine neutrophils are indeed capable of directly presenting antigen on Class II MHC and activating T cells independently of other APCs . The DO11.10-GFP hybridoma cells respond exclusively in a Class II restricted manner , and our data demonstrate that neutrophils , rather than contaminating cells , were mediating this response . At comparable cell ratios , neutrophil-mediated T cell activation was lower than that mediated by macrophages , commensurate with reduced expression of MHC Class II by neutrophils . Although neutrophils have been reported to express co-stimulatory molecules , we detected only low levels of CD40 and were unable to consistently detect CD80 or CD86 in our neutrophil preparations -LRB- in contrast to the F4/80 positive macrophages which expressed CD40 , CD80 and CD86 ; data not shown -RRB- . Thus it is possible that : co-stimulatory molecule expression below the limits of detection of methods used here is sufficient for inducing a response , that T cells are responding in a co-stimulation independent manner , or that co-stimulation has occurred via alternative molecules . Neutrophil antigen processing capacity was investigated using whole ovalbumin protein compared to OVA323 -- 339 . These studies indicated that these neutrophils did not process the ovalbumin effectively , demonstrated by a lack of response by DO11.10-GFP hybridoma -LRB- data not shown -RRB- . An MHC Class I processing pathway within neutrophils was elegantly defined with E. coli transfected to express a MHC Class I restricted epitope of OVA . This demonstrated that neutrophils are capable of non-classical antigen processing for presentation on MHC Class I -LSB- 17 -RSB- . Although neutrophil enzyme mediated degradation of collagen generates a Class II epitopes -LRB- 14 -RRB- , there is no current evidence of any Class II processing pathway . It has been proposed that as macrophage phagosomes are adequate for Class II antigen processing -LSB- 21 -RSB- , therefore a parallel system may exist in neutrophils . A definitive investigation of murine neutrophil MHC Class II antigen processing awaits transfection of bacteria with OVA323 -- 339 , thus elucidating the effects on antigen processing of concomitant neutrophil activation by bacteria . There is increasing evidence documenting the potential for neutrophils to acquire macrophage -LSB- 22 -RSB- or dendritic cell -LRB- 3 -RRB- characteristics , often in response to in vitro conditions . We document in vitro antigen presentation by in vivo activated neutrophils . It will be of interest to delineate whether such neutrophil behaviour can be observed strictly in vivo . Physiologically , the location of such neutrophil-T cell interactions is likely to be restricted to sites of chronic or established inflammation , for example persistent bacterial infection -LSB- 15 -RSB- . Neutrophils have been shown to degrade proteins to release antigens recognized by auto reactive T cells -LSB- 16 -RSB- , and such antigens may then be transported to the draining LN by migrating DCs . Due to the neutrophils ' unique proteolytic activities , this may represent a mechanism of presentation of novel or cryptic antigens . Furthermore , there is evidence that neutrophils may passively acquire membrane proteins , including MHC , from other cells -LSB- 23 -RSB- . In our GFP-hybridoma studies -LRB- Fig. 2 -RRB- , this seems unlikely as the neutrophils were harvested from the peritoneum before there was significant in vivo macrophage migration , and immediately purified in vitro . However , this phenomenon may have contributed to the neutrophil mediated T cell activation in co-culture -LRB- Fig. 3 -RRB- . There are overall fewer studies of murine neutrophils compared to human neutrophils , which is likely to be a reflection of the ease of acquiring human neutrophils that constitute 70 % of circulating leucocytes , compared to limited quantity of murine peripheral blood available and the relative paucity of neutrophils , contributing only 20 % of circulating leukocytes in rodents . These studies were only possible through use of rodent cells , as the TCR transgenic T cells absolutely control antigen specificity of response , which was central to this investigation of neutrophil-T cell interactions . However , the significantly different proportion of neutrophils in murine and human peripheral blood raises questions as to whether murine and human neutrophils perform parallel functions as is assumed . Our data document a novel , Class II restricted antigen presenting function of murine neutrophils , confirming findings in other human systems , and expanding our understanding of the role of the neutrophil in the adaptive immune response .

B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B B O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O B O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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