POS0445 DISSECTING THE ROLE OF PLATELET FUNCTION IN INFLAMMATORY ARTHRITIS

Background Inflammatory autoimmune diseases such as rheumatoid arthritis (RA) show an increase in atherosclerotic cardiovascular disease, and are commonly associated with platelet counts. Thus, platelets fill a central role the tenet: Inflammation begets coagulation, coagulation inflammation. We have previously reported that induction of by Streptococcal cell wall component peptidoglycan-polysaccharide (PGPS) results increased numbers, aggregation, activation, expression P-selectin (CD62-P) costimulatory molecule CD40. These also more sensitive to stimuli ADP thrombin, which induce dense granule release serotonin aggregation. described limited joints mice acute arthritis. Platelets, generally considered elements hemostatic system, underappreciated for their pro-inflammatory potential. Objectives To further understand inflammatory arthritis, distinguish biochemical adhesive features we set out characterize impact modulating activity chronic rodent models Methods Chronic was induced Lewis rats single i.p. injection PGPS early phase non-T dependent T after day 10. An Balb/c same method. Joint scoring volume measurement were carried daily determine severity score. The on assessed using a) depletion periodic intraperitoneal (IP) anti-platelet antibody, b) blockade integrin GPIIb/IIIa monoclonal antibody (mAb) abciximab inhibit activation aggregation via vWF fibrinogen. In murine c) deficient d) wild-type pre-treated IP anti-CD41 (GPIIb) antibody. Results Depletion during treatment resulted amelioration both phases disease. demonstrated TNF is elevated this model following injection, so comparison animals treated infliximab, TNF, equivalent suppression Abciximab, targeting dual function adhesion signaling GPIIb/IIIa, did not decrease fact model, despite CD62-P platelets, knockout had no significant difference severity. Conversely block GPIIb Conclusion Platelet dramatic unexpected given carry array procoagulant mediators including IL-1, chemokines, vWF, fibrinogen, well molecules binding endothelium, leukocytes, other platelets. inhibiting unexpected, but may been due platelet-endothelial or platelet-leukocyte thus exacerbating phase. Lack appeared influence development. Interestingly anti-CD41, blocks one part integrin, effective at ameliorating model. Platelets play often processes, understanding mechanisms will require dissection complex nature these cellular roles. Disclosure Interests Don Kimpel Speakers bureau: GSK, Consultant of: Aurinia, Krishna Kannan: None declared.