bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired cellular immune response in harbour seals (Phoca vitulina) feeding on environmentally contaminated herring
Authors: De Swart R L , Ross P S , Timmerman H H , Vos H W , Reijnders P J H , Vos J G , Osterhaus A D M E 
Published: July 2010

SUMMARYIn a 2.5-year immunotoxicological study, two groups of captive harbour seals (Phoca vitulina) were fed herring from the heavily polluted Baltic Sea or from the relatively uncontaminated Atlantic Ocean. Blood samples were collected at regular intervals, and functional immunological parameters were monitored. T cell mitogen and mixed lymphocyte-induced proliferative responses of peripheral blood mononuclear cells (PBMC) obtained from seals fed Baltic herring were significantly reduced over the course of the experiment. Upon immunization with rabies virus antigen (RV) and tetanus toxoid (TT), specific proliferative responses of PBMC from the seals fed Baltic herring were also significantly reduced. Impairment of T cell-mediated immune responses became especially apparent during the second year on the respective diets, and correlated significantly to 2,3,7,8-tetrachloro-dibenzo-p-dioxin toxic equivalent levels in blubber biopsies taken from the seals after 2 years on the respective diets. Humoral immune responses, including lipopolysaccharide (LPS)-induced lymphoproliferative responses, in vitro immunoglobulin production by PBMC, as well as RV-, TT- and poliovirus-specific serum antibody responses following immunization, remained largely unaffected. We conclude that suppression of the cellular immune response in the seals fed Baltic herring was induced by the chronic exposure to immunotoxic environmental contaminants accumulated through the food chain. Since cellular immune responses are known to be of crucial importance in the clearance of morbillivirus infections, these results suggest that environmental pollution-related immunosuppression may have contributed to the severity and extent of recent morbillivirus-related mass mortalities among marine mammals.
Cyclic AMP-elevating agents down-regulate the oxidative burst induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) in adherent neutrophils
Authors: Ottonello L , Morone M P , Dapino P , Dallegri F 
Published: July 2010

SUMMARYHuman neutrophils, plated on fibronectin-precoated wells, were found to release large quantities of superoxide anion (O2−) in response to GM-CSF. O2− production was reduced by prostaglandin E2 (PGE2) and the phosphodiesterase type IV (PDE IV) inhibitor RO 20–1724. Both agents are known to increase intracellular cyclic AMP (cAMP) levels by inducing its production (PGE.) or blocking its catabolism (RO 20–1724). When added in combination, PGE2 and RO 20–1724 had a marked synergistic inhibitory effect, which was reproduced by replacing PGE2 with a direct activator of adenylate cyclase, i.e. forskolin (FK). Moreover, the neutrophil response to GM-CSF was inhibited by a membrane-permeable analogue of cAMP in a dose-dependent manner. As GM-CSF and PGE2 are known to be generated at tissue sites of inflammation, the results suggest the existence of a PGE2-dependent regulatory pathway potentially capable of controlling the neutrophil response to GM-CSF, in turn limiting the risk of local oxidative tissue injury. Moreover, owing to its susceptibility to amplification by RO 20–1724, the PGE2-dependent pathway and in particular PDE-IV may represent a pharmacological target to reduce the generation of histotoxic oxidants by GM-CSF-responding neutrophils.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) counteracts the inhibiting effect of monocytes on natural killer (NK) cells
Authors: Van Den Bosch G , Preijers F , Vreugdenhil A , Hendriks J , Maas F , De Witte T 
Published: July 2010

SUMMARYGM-CSF is known to accelerate haematopoietic recovery following allogeneic bone marrow transplantation (BMT). In addition, it may restore and enhance both granulocyte and monocyte functions. Stimulation of monocyte functions may induce a direct or an indirect anti-leukaemic activity due to an increase of cellular cytotoxicity and production of cytokines which may result in a reduction of the relapse rate after BMT. NK cells may play a crucial role in this activity. Therefore we studied the influence of monocytes on NK activity in combination with GM-CSF. Lymphocytes and monocytes were isolated from buffy coats of healthy individuals by counterflow centrifugation elutriation (CCE). NK activity was exerted by CD3−CD56+ cell populations and could be enhanced by IL-2 incubation overnight. Incubation of CD3−CD56+ cells with GM-CSF in the presence or absence of IL-2 hardly influenced NK activity of the lymphocyte population. Low amounts of monocytes enhanced NK activity. NK activity in lymphocyte population in the presence of equivalent numbers of monocytes with or without IL-2 was strongly decreased irrespective of the effector: target ratio (ETR). This appeared not to result from sterical hindrance effects (if the present number of cells. However, addition of GM-CSF abrogated the inhibition of NK activity by monocytes in the presence of IL-2. In monocyte fractions neither IL-2 nor GM-CSF yielded NK activity. Our findings indicate that GM-CSF can affect NK activity by counteracting the suppressing effects of monocytes, and hence may improve the outcome after BMT.
Defective functional response to membrane stimuli in lymphocytes from patients with benign prostatic hyperplasia
Authors: PÉRez-Blas M , MartÍNez-MartÍN B , Carballido J , Hontoria J , Salazar L I , Olivier C , Alvarez-Mon M 
Published: July 2010

SUMMARYBenign prostatic hyperplasia (BHP) is a local disturbance in the prostate that may involve an inflammatory infiltrate predominantly composed of activated lymphocytes and macrophages. The activation and proliferative response of T lymphocytes to different mitogenic signals has been analysed in peripheral blood mononuclear cells (PMBC) from 45 patients with BHP and 55 healthy controls. The PBMC obtained from the patients showed a significant specific impairment in proliferation, CD25 expression and IL-2 production in response to stimulation with lectins (phytohaemagglutinin (PHA), concanavalin A (Con A)), that was not corrected by the addition of IL-2 or of phorbol esters (phorbol myristate acetate (PMA)). Also, the CD28 response was defective in patient PBMC. Activation with anti-CD3 or anti-CD2 MoAbs was normal, but the addition of PMA to these stimuli provoked a significant defective response. Only the use of transmembrane stimuli (PMA and ionomycin) elicited responses similar to those found in the control group. The results indicate that peripheral T lymphocytes from BPH patients show a functional impairment that is mainly explained by an alteration of membrane signals (PHA, CD28) and is distal to protein kinase C (PKC) activation.
Failure of IgG production due to a defect in the opening of the chromatin structure of Iγ1 region in a patient with IgG and IgA deficiency
Authors: Kondo N , Inoue R , Kasahara K , Kaneko H , Kameyama T , Orii T 
Published: July 2010

SUMMARYPatients with common variable immunodeficiency (CVID) display reduced levels of two or all three of the major immunoglobulin isotypes, and the deficiency is characterized by failure of B cells to differentiate into plasma cells in many cases. A patient (14 years old, female) showed normal serum IgM levels and low serum IgG and IgA levels, including low levels of all IgG subclasses. Northern blot analysis suggested that the patient's B cells may be defective at the immunoglobulin heavy chain isotype switch. The germ-line Cγ1 transcript was amplified from cDNA of healthy controls by the addition of recombinant IL-2 (rIL-2) to pokeweed mitogen-stimulated peripheral mononuclear cells or Staphylococcus aureus Cowan I (SAC)-stimulated IgM-producing lymphoblastoid cell lines (LCL) transformed by Epstein-Barr virus, while it was not amplified from cDNA of the patient. In the Iγ1 region of LCL cultured with SAC plus rIL-2, the inner cytosine in the 5′C-C-G-G 3′sequence nearest the 3′site of the Iγ1 region, at least, was not completely unmethylated in the patient. Moreover, the DNase I hypersensitive site was not induced in the patient's LCL by SAC plus rIL-2. These results indicate that the defects of the immunoglobulin heavy chain isotype switch in the patient's B cells are due to failure in the synthesis of germ-line Cγ transcripts, and this may be caused by defects in opening of the chromatin structures of specific switch regions.
A role for IL-4 in immunologically mediated enteropathy
Authors: Mowat A MCI , Widmer M B 
Published: July 2010

SUMMARYA number of clinical enteropathies are associated with a local cell-mediated immune (CMI) response, and experimental evidence indicates that cytokines are responsible for the intestinal pathology. We show here that depletion of IL-4 using MoAb or a soluble form of the IL-4 receptor (IL-4R) prevents the jejunal manifestations of a proliferative form of murine graft-versus-host reaction (GVHR) characterized by crypt hyperplasia and recruitment of intraepithelial lymphocytes (IEL). Depletion of IL-4 did not prevent the appearance of villus atrophy in a destructive model of GVHR, and had no effect on any indices of systemic immunity. These results indicate that IL-4 may play a selective role in mediating proliferative aspects of intestinal immunopathology, and suggest that this cytokine may provide a useful target for immunotherapy.
Interferon-gamma (IFN-γ) production by human T lymphocytes uponLegionella pneumophilastimulationin vitro
Authors: Kitsukawa K , Nakamoto A , Koito H , Matsuda Y , Saito A , Yamamoto H 
Published: July 2010

SUMMARYIn vitro immune responses to Legionella pneumophila were investigated. When human peripheral blood lymphocytes (PBL) from healthy volunteers were stimulated with formalin-killed L. pneumophila for 7 days in vitro, strong proliferative responses were observed. The responding cells were shown to be a CD4a T cell subset. It was also found that the CD4 T cells secreted significant amounts of IFN-γ into the PBL culture supernatant. The production of IFN-γ and IL-4 by PBL was measured semiquantitatively by reverse transcriptase-assisted polymerase chain reaction (RT-PCR) methods. Formalin-killed or live L. pneumophila- stimulated PBL expressed the mRNA for IFN-γ but not the mRNA for IL-4. The results suggest that the whole bacterium, as opposed to the supernatant, predominantly stimulates Th1 type helper T cells. The cloned T cells specific for L. pneumophila expressed the mRNA for IFN-γ but not for IL-4. In contrast to formalin-killed or live L. pneumophila stimulation, when PBL were stimulated with the bacterial culture supernatant, the proliferating T cells produced the mRNA for IL-4 as well as for IFN-γ. A significant correlation between the proliferative response to formalin-killed L. pneumophila and IFN-γ release in culture was observed (r= 0.6932, P 0.001) in PBL from 30 healthy volunteers. From these in vitro studies, it is suggested that the whole L. pneumophila bacterium and their soluble antigens stimulate T cells in a manner which results in a different pattern of cytokine production.
IL-8 release from cultured peripheral blood monocytes of patients with glomerulonephritis
Authors: Matsumoto K 
Published: July 2010

SUMMARYIL-8 is a chemotactic cytokine with proinflammatory and growth-promoting activities. The release of IL-8 was measured in supernatants of cultured peripheral blood monocytes (PBM) that were obtained from patients with glomerulonephritis (GN) and healthy controls. Spontaneous and lipopoly-saccharide (LPS)-induced IL-8 release was significantly higher in PBM isolated from patients with IgA nephropathy (IgAN) and membranous nephropathy (MN) compared with normal controls. These results raise the question of whether IL-8 contributes to the ongoing pathogenesis of GN, We cannot relate IL-8 release to clinical and laboratory parameters in IgAN and MN patients. Thus, disease progression in vivo may not be accompanied by increased or sustained IL-8 release.
Longer local retention of adoptively transferred T-LAK cells correlates with lesser adhesion molecule expression than NK-LAK cells
Authors: YAMAMOTO T , YONEDA K , OSAKI T , YOSHIMURA N , AKAGI N 
Published: July 2010

SUMMARYThe local retention of adoptively transferred lymphokine (IL-2)-activated killer (LAK) cells was examined in 11 patients with head and neck carcinoma. Unseparated lymphocytes, T and natural killer (NK) cells isolated from patients were cultured with IL-2 for 7 days, labelled with 99mTc-HMPAO, and immediately injected back into the respective donors via the superficial temporal artery or locally into the tumour tissue. The injected LAK cells were periodically traced using a gamma camera, and the LAK cell retention rate was calculated from the radioactivity. One hour after the injection, about 70% of the locally infiltrated LAK cells remained in the tumour tissue, while about half of the LAK cells transferred via the regional artery were dislodged from the tissue. LAK cells induced from T cells (T-LAK) were retained in the tissue for a longer time than LAK cells induced from NK cells (NK-LAK). T-LAK were less chemotactic and less adherent to human umbilical vein endothelial cells (EC), and showed lesser migration through EC. Flow cytometric analysis revealed higher expression of CD11a, CD11b, CD18 and CD49d on NK-LAK compared with T-LAK. MoAbs against these adhesion molecules suppressed adhesion and migration of LAK cells. These results indicate that the rapid disappearance of NK-LAK from the tissue is associated with their greater chemotactic and adhesive as well as migratory activities depending on differing expression of adhesion molecules.
Effect of postponed treatment with an anti-tumour necrosis factor (TNF) F(ab')2 fragment on endotoxin-induced cytokine and neutrophil responses in chimpanzees
Authors: VAN DER POLL T , LEVI M , CATE H TEN , JANSEN J , BIEMOND B J , HAAGMANS B L , EERENBERG A , VAN DEVENTER S J H , HACK C E , CATE J W TEN 
Published: July 2010

SUMMARYTNF is considered to be an intermediate factor in endotoxin-induced release of other cytokines and endotoxin-induced neutrophil degranulation. Little is known about the effect of postponed treatment with anti-TNF in primate endotoxin models. To assess the effect of delayed treatment with anti-TNF in endotoxaemia, six healthy adult chimpanzees were intravenously injected with Escherichia coli endotoxin (4 ng/kg). In three of these animals the administration of endotoxin was followed after 30 min by a bolus i.v. injection of the anti-TNF F(ab')2 fragment MAK 195F (0.1 mg/kg). Post-treatment with MAK 195F completely prevented the appearance of TNF activity in serum elicited by endotoxin, and markedly reduced the rises in the serum concentrations of IL-6 and IL-8. In addition, the endotoxin-induced increases in the type I and type II soluble TNF receptors were also profoundly inhibited by MAK 195F, suggesting that TNF is involved in the release of its own soluble receptors in endotoxaemia, Neutrophilic leucocytosis was not affected by MAK 195F. In contrast, MAK 195F did significantly abrogate neutrophil degranulation, as measured by the plasma concentrations of lactoferrin. These results indicate that treatment with anti-TNF 30 min after the administration of endotoxin is still effective in attenuating the induction of the cytokine network and of neutrophil degranulation.
Vaccination of patients deficient in a late complement component with tetravalent meningococcal capsular polysaccharide vaccine
Authors: PLATONOV A E , BELOBORODOV V B , PAVLOVA L I , VERSHININA I V , KÄYHTY H 
Published: July 2010

SUMMARYEighteen patients with late complement component deficiency (LCCD) were immunized with meningococcal capsular polysaccharide vaccine. The LCCD patients had experienced one-to-five meningococcal infections before vaccination, but their immunological and clinical status was normal at the time of immunization. Serum samples from vaccinated complement-sufficient relatives of the LCCD patients and healthy Russian male adults were used as controls. Total and immunoglobulin-specific concentrations of antibodies to group A, C, W135, and Y capsular polysaccharides were determined by enzyme immunoassay in serum samples taken before and 1–108 weeks after immunization. The individual preimmunization and post-immunization antibody concentrations varied greatly. The median antibody concentrations of the LCCD patients increased significantly after vaccination, and were not significantly different from those of the control groups. The antibody concentrations remained elevated for at least 1 year after vaccination. The post-immunization antibody concentrations correlated with the number of meningococcal infections within 10 years before vaccination. In spite of the vaccination two LCCD patients experienced a meningococcal disease 9 and 12 months, respectively, after vaccination.
The kinetics and distribution of C9 and SC5b-9in vivo: effects of complement activation
Authors: GREENSTEIN J D , PEAKE P W , CHARLESWORTH J A 
Published: July 2010

SUMMARYMany diseases associated with complement activation are characterized by tissue deposition of components of the terminal complement complex (TCC). The ninth component of complement (C9) plays an important role in the cytolytic effects, and may contribute to the non-lethal cell-regulating functions of the TCC [1]. In this study we examined the behaviour of radiolabelled human C9 and its soluble complexed form SC5b-9 in vivo in order to determine the effects of complement activation on its turnover, distribution and molecular size. In normal rabbits the metabolic parameters of 125I-C9 (median and range) were: plasma half-life (t1/2) 25.9 (20.6-29.5) h, fractional catabolic rate (FCR) 5.7 (5.3-7.0)%/h, and extravascular/intravascular ratio (EV/IV) 0.7 (0.6-1.1). The distribution of radiolabelled C9 amongst body tissues was similar to that observed for rabbit serum albumin (RSA). Activation of the complement cascade with i.v. injection of cobra venom factor (CVF) resulted in rapid disappearance of C9 from the plasma and accumulation of protein-bound radiolabel in the spleen (exceeding the plasma concentration) and the liver. RSA metabolism and distribution were unaffected by CVF. Fine performance liquid chromatography (FPLC) gel filtration of plasma samples suggested that monomeric C9 was the only major radiolabelled protein present during normal turnovers, whereas CVF administration was accompanied by the prompt appearance of a high mol. wt species consistent in size with SC5b-9. When injected directly, 125I-SC5b-9 disappeared rapidly from the plasma, falling by 50% in 0.7 (0.6-0.8) h, and less than 15% remaining after 4 h with accumulation of protein-bound label in the spleen and liver. These results demonstrate the complexity of C9 metabolism during complement activation.
Dendritic cells in synovial fluid of chronic inflammatory arthritis lack CD80 surface expression
Authors: SUMMERS K L , DANIEL P B , O'DONNELL J L , HART D N J 
Published: July 2010

SUMMARYDendritic cells (DC) act as potent primary antigen-presenting cells in many immune responses and therefore may have a role in the initiation and perpetuation of the synovial inflammation in chronic inflammatory arthritis. To examine their function, it is important to isolate fresh DC from arthritic joints without aberrant activation. We have developed a technique using minimal cell manipulation to isolate DC from the synovial fluid of chronic arthritic patients. Using this method, DC were shown to be potent allostimulatory cells, with 63–90% of cells lacking lineage-specific markers (lin-), but positive for MHC class II molecules. Two morphologically distinct populations of these cells were identified in 10 out of 13 DC preparations. Both populations expressed CD40, intercellular adhesion molecule-1 (ICAM-1), ICAM-2, ICAM-3 and leucocyte function associated antigen-3 (LFA-3), but the predominant population, which was larger and more typical of cultured blood DC, had a higher density of these antigens compared with the minor population, which were smaller and morphologically similar to lymphocytes. Two new MoAbs which label activated human blood DC, HB15 (CD83) and CMRF-44, were tested. CD83 labelled very weakly or not at all, whereas CMRF-44 was positive on the larger cells only. Likewise, the costimulator molecule, B7/BB1 (CD80), was not detected on the surface of either synovial lin- cell population, reverse transcriptase polymerase chain reaction (RT-PCR) showed little or no CD80 mRNA, and no binding of the CTLA-4Ig fusion protein was found. These results suggest that synovial DC are not, despite the inflammatory environment, in a fully activated state.
The rheumatoid arthritis-associated autoantibodies to filaggrin label the fibrous matrix of the cornified cells but not the profilaggrin-containing keratohyalin granules in human epidermis
Authors: SIMON M , VINCENT C , HAFTEK M , GIRBAL E , SEBBAG M , GOMÈS-DAUDRIX V , SERRE G 
Published: July 2010

SUMMARY
Since they were first described, serum IgG antibodies to the stratum corneum of rat oesophagus epithelium, highly specific for rheumatoid arthritis (RA), have been consensually called anti-keratin antibodies (AKA). However, we recently demonstrated that they actually recognize three new proteins of rat oesophagus epithelium distinct from cytokeratins, and also human epidermal filaggrin. In this work we provided further evidence that AKA and RA-associated anti-filaggrin autoantibodies are the same antibodies. Moreover, analysing by indirect immunofluorescence on human skin a large series of 212 well characterized RA sera and anti-filaggrin autoantibodies purified from RA sera by affinity chromatography. we demonstrated the specific binding of AKA to the stratum corneum of human epidermis and the absence of any staining of the granular keratinocytes. This binding was confirmed and the AKA antigen precisely localized in human epidermis by immunoelectron microscopy. The antigen was found to be restricted to the filaggrin-containing intracellular fibrous matrix of the corneocytes, up to the desquamating cells. In contrast, MoAbs directed to human filaggrin and to profilaggrin, its precursor, not only stained the intracellular matrix of the tower corneocytes but also the keratohyatin granules of the granular cells, where profilaggrin is stored. These results reinforced by the absence of immunoblotting reactivity of RA sera to profilaggrin suggest that the epitopes recognized by AKA are absent from profilaggrin. Their identification may provide more insight into the pathogenesis of RA.