Journal
SCIENCE
Volume 327, Issue 5965, Pages 580-583Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1181928
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Funding
- NIH [P01 AI065858, K08AR051321, HL091269]
- Arthritis Foundation
- Cogan Family Foundation
- British Heart Foundation and Medical Research Council, UK
- National Heart, Lung, and Blood Institute [HL50545]
- MRC [G0500707] Funding Source: UKRI
- British Heart Foundation [RG/09/003/27122] Funding Source: researchfish
- Medical Research Council [G0500707] Funding Source: researchfish
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In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles-submicrometer vesicles elaborated by activated platelets-in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases.
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