Platelets participate in synovitis via Cox-1–dependent synthesis of prostacyclin independently of microparticle generation

E Boilard, K Larabee, R Shnayder… - The Journal of …, 2011 - journals.aai.org
E Boilard, K Larabee, R Shnayder, K Jacobs, RW Farndale, J Ware, DM Lee
The Journal of Immunology, 2011journals.aai.org
In addition to the well-described role of platelets in thrombosis, a growing body of evidence
implicates platelets in diverse inflammatory responses. We recently showed platelets can
contribute to the pathophysiology of inflammatory arthritis via IL-1–containing microparticles.
In this study, we demonstrate that platelets, and not platelet microparticles, actively
contribute to synovitis via production of proinflammatory prostacyclin in an autoimmune
arthritis model. Using both genetic and pharmacologic approaches, we establish that …
Abstract
In addition to the well-described role of platelets in thrombosis, a growing body of evidence implicates platelets in diverse inflammatory responses. We recently showed platelets can contribute to the pathophysiology of inflammatory arthritis via IL-1–containing microparticles. In this study, we demonstrate that platelets, and not platelet microparticles, actively contribute to synovitis via production of proinflammatory prostacyclin in an autoimmune arthritis model. Using both genetic and pharmacologic approaches, we establish that paracrine production of prostacyclin proceeds in the absence of cyclooxygenase-2. Furthermore, we also demonstrate that prostacyclin generation can arise via transcellular collaboration between platelets and fibroblast-like synoviocytes. In addition to shedding light on an unappreciated pathway of lipid synthesis in arthritis, we further delineate a novel effector activity by which platelets can contribute to inflammatory disease.
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