Microparticle-induced release of B-lymphocyte regulators by rheumatoid synoviocytes.
BACKGROUND
In the present study, we investigated the ability of microparticles isolated from synovial fluids from patients with rheumatoid arthritis or osteoarthritis to induce the synthesis and release of key cytokines of B-lymphocyte modulation such as B cell-activating factor, thymic stroma lymphopoietin, and secretory leukocyte protease inhibitor by rheumatoid fibroblast-like synoviocytes.


METHODS
Microparticles were analyzed in synovial fluids from patients with rheumatoid arthritis, osteoarthritis, microcristalline arthritis, and reactive arthritis. In addition, microparticle release after activation from various cell lines (CEM lymphocyte and THP-1 cells) was assessed. Microparticles were isolated by differential centrifugation, and quantitative determinations were carried out by prothrombinase assay after capture on immobilized annexin V. B cell-activating factor, thymic stroma lymphopoietin, and secretory leukocyte protease inhibitor release was evaluated by enzyme-linked immunosorbent assay.


RESULTS
Microparticles isolated from synovial fluids obtained from rheumatoid arthritis and osteoarthritis patients or microparticles derived from activated THP-1 cells were able to induce B cell-activating factor, thymic stroma lymphopoietin, and secretory leukocyte protease inhibitor release by rheumatoid arthritis fibroblast-like synoviocytes. Conversely, CEM-lymphocytes-derived microparticles generated by treatment with a combination of PHA, PMA and Adt-D did not promote the release of B cell-activating factor but favored the secretion of thymic stroma lymphopoietin and secretory leukocyte protease inhibitor by rheumatoid arthritis fibrobast-like synoviocytes. However, microparticles isolated from actinomycin D-treated CEM lymphocytes were not able to induce B cell-activating factor, thymic stroma lymphopoietin, or secretory leukocyte protease inhibitor release, indicating that microparticles derived from apoptotic T cells do not function as effectors in B-cell activation.


CONCLUSIONS
These results demonstrate that microparticles are signalling structures that may act as specific conveyors in the triggered induction and amplification of autoimmunity. This study also indicates that microparticles have differential effects in the crosstalk between B lymphocytes and target cells of autoimmunity regarding the parental cells from which they derive.
Messer
Laurent
L
Laboratoire Physiopathologie des Arthrites, Université de Strasbourg, UFR Sciences Pharmaceutiques, Illkirch, France. laurentmesser@yahoo.fr
Alsaleh
Ghada
G
Freyssinet
Jean-Marie
JM
Zobairi
Fatiha
F
Leray
Isabelle
I
Gottenberg
Jacques-Eric
JE
Sibilia
Jean
J
Toti-Orfanoudakis
Florence
F
Wachsmann
Dominique
D
D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D055252:Cell-Derived Microparticles / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020239:Receptor Cross-Talk / Q000276:immunology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000096:biosynthesis / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology*; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
D053264:B-Cell Activating Factor; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D000094632:Thymic Stromal Lymphopoietin