Proposed Pathway for GPVI-Dependent Participation of Platelets in Arthritis via Microparticles. GPVI-expressing platelets activated by collagen produce copious amounts of IL-1-rich microparticles (MPs) (left panel and inset). The precise anatomic location of platelet activation and the route by which microparticles enter the joint (dotted red line in the left side of the figure where the microparticles are going across the synovial lining) remain unknown. Platelet MPs (~0.2-1 μm in diameter), detectable at high levels in inflammatory synovial fluid, interact with tissue cells including fibroblast-like synoviocytes (FLS) and synovial fluid leukocytes (right panel). This interaction elicits further inflammatory effector functions from target cells, thereby amplifying synovitis. In the case of FLS, platelet MPs promote elaboration of IL-8 and other mediators that are capable of leukocyte chemoattraction to the joint (right panel). Platelet microparticles attached to neutrophils, as found in diseased synovial fluid, may also stimulate neutrophil effector functions, although this remains to be established (question mark, right panel). Figure courtesy of S. Moskowitz and D. Lee.