Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production

被引：875

作者：

Boilard, Eric ^{[1
]}

Nigrovic, Peter A. ^{[1
,2
]}

Larabee, Katherine ^{[1
]}

Watts, Gerald F. M. ^{[1
]}

Coblyn, Jonathan S. ^{[1
]}

Weinblatt, Michael E. ^{[1
]}

Massarotti, Elena M. ^{[1
]}

Remold-O'Donnell, Eileen ^{[3
]}

Farndale, Richard W. ^{[4
]}

Ware, Jerry ^{[5
]}

Lee, David M. ^{[1
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA

[2] Childrens Hosp Boston, Div Immunol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA

[4] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England

[5] Univ Arkansas Med Sci, Little Rock, AR 72205 USA

来源：

SCIENCE | 2010年 / 327卷 / 5965期

基金：

英国医学研究理事会;

关键词：

RHEUMATOID-ARTHRITIS; GLYCOPROTEIN-VI; ACTIVATION; DISEASE; COMPLEXES; MECHANISM; RECEPTOR; PLASMA; CHAIN;

D O I：

10.1126/science.1181928

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：580 / 583

页数：4