Platelets amplify inflammation in arthritis via collagen-dependent microparticle production.
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.
Boilard
Eric
E
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Nigrovic
Peter A
PA
Larabee
Katherine
K
Watts
Gerald F M
GF
Coblyn
Jonathan S
JS
Weinblatt
Michael E
ME
Massarotti
Elena M
EM
Remold-O'Donnell
Eileen
E
Farndale
Richard W
RW
Ware
Jerry
J
Lee
David M
DM
D000818:Animals; D001168:Arthritis / Q000097:blood / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D038981:Receptors, Collagen / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology*; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology
D016207:Cytokines; D007375:Interleukin-1; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI; D003094:Collagen