Enhanced Fcgamma receptor I, alphaMbeta2 integrin receptor expression by monocytes and neutrophils in rheumatoid arthritis: interaction with platelets.
ABSTRACT To investigate platelet and leukocyte activation and interaction in patients with rheumatoid arthritis (RA) and the effect of methotrexate (MTX) or anti-tumor necrosis factor-a (TNF-a) treatment on these variables.
Four-color flow cytometry analysis was performed for quantitative measurement of platelet (P-selectin, PAC-1) and leukocyte (CD11b, CD64) activation markers and estimation of percentage of leukocyte-platelet complexes in whole blood in 20 patients with RA before and after 6 weeks of therapy and in 20 controls. In addition, measures of soluble P-selectin (sP-selectin), beta-thromboglobulin, fibrinogen, prothrombin fragment 1+2, D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), and TNF-a and tender and swollen joint counts were carried out.
Before therapy, PAC-1 binding, expression of CD11b and CD64 on monocytes and neutrophils, circulating levels of monocyte (CD11b+ or CD64+)-platelet complexes, monocyte-PAC-1+ platelet complexes, CRP, ESR, IL-6, TNF-a, fibrinogen, D-dimer and sP-selectin were significantly higher in RA patients compared to controls. The anti-TNF-a therapy significantly reduced levels of monocyte-PAC-1+ platelet complexes, sP-selectin, CRP, ESR, IL-6, TNF-a, fibrinogen, and D-dimer and tender and swollen joint counts. CD64 expression on monocytes was significantly decreased by MTX therapy. PAC-1 binding was not inhibited by MTX or anti-TNF-a.
Increased platelet and leukocyte activation and increased formation of leukocyte-platelet complexes in patients with RA suggest a status of simultaneous activation of the immune and hemostatic systems.
SourceAvailable from: Véronique Ollivier[Show abstract] [Hide abstract]
ABSTRACT: There is now a large body of evidence that platelets are central actors of inflammatory reactions. Indeed, platelets play a significant role in a variety of inflammatory diseases. These diseases include conditions as varied as atherosclerosis, arthritis, dermatitis, glomerulonephritis, or acute lung injury. In this context, one can note that inflammation is a convenient but imprecise catch-all term that is used to cover a wide range of situations. Therefore, when discussing the role of platelets in inflammation, it is important to clearly define the pathophysiological context and the exact stage of the reaction. Inflammatory reactions are indeed multistep processes that can be either acute or chronic, and their sequence can vary greatly depending on the situation and organ concerned. Here, we focus on how platelets contribute to inflammatory reactions involving recruitment of neutrophils and/or macrophages. Specifically, we review past and recent data showing that platelets intervene at various stages of these reactions to regulate parameters such as endothelial permeability, the recruitment of neutrophils and macrophages and their effector functions, as well as inflammatory bleeding. The mechanisms underlying these various modulating effect of platelets are also discussed.Frontiers in Immunology 01/2014; 5:678. DOI:10.3389/fimmu.2014.00678
Article: Platelets Are Not Just for Clots[Show abstract] [Hide abstract]
ABSTRACT: Whilst the role of platelets as central mediators of haemostasis and thrombosis has been the primary focus of research into platelet biology for over a century, over the last decade, non-haemostatic functions of platelets have been increasingly defined. As such, a large body of experimental evidence now exists which places the platelet as a key player in mediating a diverse range of immune, inflammatory and malignant disease processes. This review outlines the central mechanisms which underpin the non-haemostatic role of platelets and provides a summary of the evidence demonstrating a role for platelets in mediating selected inflammatory, immune and malignant disease processes.Transfusion Medicine Reviews 01/2015; DOI:10.1016/j.tmrv.2014.11.006 · 4.54 Impact Factor
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ABSTRACT: Given the critical role of Fc gamma receptors (FcγR) as primary targets for autoantibody-mediated effects an important issue is how the FcγR pathway is affected in autoimmune disorders. Here we investigated the FcγR function in monocytes from rheumatoid arthritis (RA) patients in relation to immunoglobulin levels and disease activity. Peripheral blood was obtained from 30 RA patients with clinical acute joint synovitis (active RA), 28 RA patients with no clinical signs of acute joint synovitis (non-active RA) and 34 healthy controls. Prior the functional studies the monocytes were characterized of their FcγRI (CD64), II (CD32), IIb (CD32b) and III (CD16) expression as well as their cell surface bound IgG. The monocytic FcγR function was assessed by binding of human IgG1 and IgG3 immune complexes (IC) and TNF secretion in vitro. IgG anti-citrullinated peptide antibodies (ACPA) were analyzed in the plasma. We found that monocytes from active RA patients had increased levels of FcγRI, II and cell surface IgG concurrently with impaired FcγR function. This was evident by reduced IgG1-IC binding and decreased TNF secretion in response to IgG3-IC. In contrast, monocytes from non-active RA patients displayed a normal FcγR function and had increased FcγRIIb expression together with elevated FcγRI, II and cell surface IgG. The ACPA levels did not differ in active and non-active RA patients but correlated with the monocytic FcγRIII expression in the patients. In conclusion, active RA patients display a dysregulated FcγR function that may represent a novel phenotypic and likely pathogenetic marker for active RA. A disease and FcγR function controlling effect is suggested by the increased inhibitory FcγRIIb in non-active RA.Immunology Letters 09/2014; DOI:10.1016/j.imlet.2014.08.016 · 2.37 Impact Factor