Clinical trial NCT01099410: Apoptotic Cell (AC) Uptake by Human Alveolar Macrophages (AM)
Official title: Apoptotic Cell Ingestion by Normal Human Alveolar Macrophages
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: macrophages, alveolar
monocytes
Receptor Protein-Tyrosine Kinases
Humans
Phagocytosis
Lung
in vitro
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2010-04-07
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Volunteer subjects recruited from the community; may be current or ex-smokers or never-smokers, but must be healthy enough to undergo research bronchoscopy safely.

Brief summary: The purpose of this study is to compare the ability of two types of white blood cells to eat dead host cells, and how this process affects their ability to protect the body from infection. The two cell types are monocytes, a cell in the bloodstream, and alveolar macrophages, a cell in the lung that is ultimately derived from monocytes

Detailed description: Volunteers, who may be Veterans or non-Veterans, will be screened by a series of questionnaires, chest X-ray, spirometry, EKG, blood work, and a complete history and physician examination by a study physician. Those who qualify for the study and agree via informed consent, will undergo a fiberoptic bronchoscopy on a separate day for the initial visit. Bronchoscopy is a procedure in which a flexible video instrument is passed via the nose or mouth, through the vocal cords and into the lungs. During the procedure, portions of the lungs will be washed ("lavaged") with a salt water solution, to collect the alveolar macrophages. This procedure involves conscious sedation, so that a driver is required on the day of the bronchoscopy. The entire procedure, including placement of an intravenous line to administer medications, local anesthetics, the bronchoscopy itself, and the recovery period, takes about 2.5-3 hours. The cells collected by bronchoscopy will be studied in the research laboratory, and used entirely in that procedure.

Eligibility criteria: Inclusion Criteria:

* Veteran or non-Veteran
* Able to give informed consent

Exclusion Criteria:

* Unstable heart disease
* Other systemic disease and unlikely to survive at least 2 years
* Mental incompetence
* Prednisone \>20 mg/day
* Participation in another interventional protocol within last 6 weeks
* Asthma
* Cystic fibrosis
* Clinically significant bronchiectasis
* Lung cancer or any cancer not in remission for at least 5 years
* Other inflammatory or fibrotic lung disease
* Use of antibiotics for a lung infection within the past 4 weeks
* Autoimmune disease, i.e., Rheumatoid arthritis, systemic lupus erythematosus, autoimmune hepatitis, Crohn's disease or other

Primary outcomes:
measure: macrophage uptake of apoptotic cells in vitro
timeFrame: 1-7 days
Secondary outcomes:
measure: spirometric measurement of lung function
timeFrame: 1-30 days
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System, Ann Arbor, MI
state: Michigan
Study officials:
affiliation: VA Ann Arbor Healthcare System, Ann Arbor, MI
name: Jeffrey L Curtis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bourdonnay E, Zaslona Z, Penke LR, Speth JM, Schneider DJ, Przybranowski S, Swanson JA, Mancuso P, Freeman CM, Curtis JL, Peters-Golden M. Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling. J Exp Med. 2015 May 4;212(5):729-42. doi: 10.1084/jem.20141675. Epub 2015 Apr 6.
citation: Todt JC, Freeman CM, Brown JP, Sonstein J, Ames TM, McCubbrey AL, Martinez FJ, Chensue SW, Beck JM, Curtis JL. Smoking decreases the response of human lung macrophages to double-stranded RNA by reducing TLR3 expression. Respir Res. 2013 Mar 9;14(1):33. doi: 10.1186/1465-9921-14-33.