Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Science. 2010 Jan 29;327(5965):580-3. 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.
除了在血栓形成和伤口修复中发挥关键作用外，血小板还参与炎症反应。我们研究了血小板在自身免疫性疾病类风湿关节炎中的作用。我们在类风湿关节炎和其他形式的炎症性关节炎患者的关节液中发现了血小板微粒——由活化的血小板产生的亚微米囊泡，但在骨关节炎患者的关节液中没有发现。血小板微粒具有促炎作用，通过白细胞介素-1引起滑膜成纤维细胞产生细胞因子反应。这些发现与以下发现一致：血小板耗竭可减轻小鼠炎症性关节炎。我们使用药理学和遗传学方法，确定胶原受体糖蛋白 VI 作为关节炎病理生理学中血小板微粒生成的关键触发因素。因此，这些发现表明血小板及其激活诱导的微粒在炎症性关节疾病中具有以前未被认识到的作用。
