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Science 327 (5965): 580-583

Copyright © 2010 by the American Association for the Advancement of Science

Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production

Eric Boilard,1 Peter A. Nigrovic,1,2 Katherine Larabee,1 Gerald F. M. Watts,1 Jonathan S. Coblyn,1 Michael E. Weinblatt,1 Elena M. Massarotti,1 Eileen Remold-O’Donnell,3 Richard W. Farndale,4 Jerry Ware,5 David M. Lee1,*

Abstract: 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.

1 Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
2 Division of Immunology, Children’s Hospital Boston, Boston, MA 02115, USA.
3 Immune Disease Institute, Harvard Medical School, Boston MA 02115, USA.
4 University of Cambridge, Department of Biochemistry, Downing Site, Cambridge CB2 1QW, UK.
5 University of Arkansas for Medical Sciences, Little Rock, AR 72205–7199, USA.

* To whom correspondence should be addressed. E-mail: dlee{at}rics.bwh.harvard.edu

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