Proposed pathway for the formation of gaps and amplification of the vasculature permeability by platelets during arthritis. Top panel: Gaps between endothelial cells in arthritic joints are formed. The GPVI-expressing platelets are activated by the newly exposed subendothelial matrix rich in GPVI ligands, such as collagen and laminin. Bottom panel: Stimulated platelets produce copious amounts of IL-1–rich microparticles and release serotonin. Platelet-derived serotonin promotes the production of additional gaps; thus, more platelets can be activated. Serotonin at the site of inflammation promotes the vasculature leakage during disease. Note that the precise anatomic location of platelet activation and the route by which microparticles enter the joint remain speculative. ▴ represents serotonin; and ○, platelet microparticle. Illustration courtesy of Steve Moskowitz, Advanced Medical Graphics.