Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production

• Published in: Science (American Association for the Advancement of Science) Vol. 327; no. 5965; pp. 580 - 583
• Main Authors: Boilard, Eric, Nigrovic, Peter A, Larabee, Katherine, Watts, Gerald F.M, Coblyn, Jonathan S, Weinblatt, Michael E, Massarotti, Elena M, Remold-O'Donnell, Eileen, Farndale, Richard W, Ware, Jerry, Lee, David M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 29-01-2010; The American Association for the Advancement of Science
• Subjects: Animals; Arthritis; Arthritis - blood; Arthritis - immunology; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - physiopathology; Biological and medical sciences; Blood clots; Blood Platelets - cytology; Blood Platelets - physiology; Blood Platelets - ultrastructure; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - physiology; Cells, Cultured; Collagen - metabolism; Collagens; Cytokines; Cytokines - metabolism; Cytometry; Diseases of the osteoarticular system; Extracellular Matrix - metabolism; Fibroblasts - immunology; Fibroblasts - metabolism; Humans; Immune system; Inflammation; Inflammatory joint diseases; Interleukin-1 - metabolism; Joints; Leukocytes; Medical sciences; Mice; Mice, Transgenic; Miscellaneous. Osteoarticular involvement in other diseases; Neutrophils; Osteoarthritis; Platelet Activation; Platelet Membrane Glycoproteins - metabolism; Platelets; Proteins; Receptors, Collagen - metabolism; Rheumatoid arthritis; Synovial Fluid - cytology; Synovial Fluid - immunology; Synovial Membrane - cytology; Synovial Membrane - immunology; Human; Immunopathology; Diseases of the osteoarticular system; Cardiovascular disease; Autoimmune disease; Arthritis; Inflammation; Inflammatory joint disease; Joint; Wound; Thrombosis; Vascular disease; Chronic; Platelet; Synovial membrane; Animal; Inflammatory arthritis; Collagen; Rheumatoid arthritis; Arthropathy; Degenerative disease; Osteoarthritis; Fibroblast
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1181928

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.