Functions of Platelet Microparticles in Inflammatory Arthritis

Abstract SCI-35

Besides their pivotal role in thrombosis and wound repair, platelets can participate in inflammatory responses via a broad arsenal that includes CD40L and CD40, cyclooxygenase-1 mediated prostaglandins, leukotrienes, IL-1, RANTES, serotonin, platelet factor 4, matrix metalloproteinases -2 and -9, P-selectin, adenosine diphosphate, and reactive oxygen species. Rheumatoid arthritis (RA) is amongst the most common autoimmune chronic inflammation that affects the joints. Interestingly, we found copious amounts of submicron particles that harbor platelet integrins in the synovial fluid of patients suffering from RA, pointing to evidence of platelet activation in this inflammatory autoimmune disease. Importantly, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. In addition to the transcellular collaboration between platelets and fibroblast-like synoviocytes in generation of pro-inflammatory prostacyclin (1), we found that platelets contribute to synovitis by production of IL-1-rich platelet microparticles (2). These recent advances in understanding of the platelet activities in inflammation notwithstanding, the mechanisms by which platelet microparticles invade the diseased joint in RA remain obscure. Using synovial biopsies from patients suffering from RA in addition to in vivo imaging strategies in a murine model of arthritis, our current work aspires to dissect the means of transportation of platelet microparticles during RA. Given their pro-inflammatory properties, to understand the process by which microparticles invade the synovial joint is of great clinical interest.