Platelets: active players in the pathogenesis of arthritis and SLE

• Published in: Nature reviews. Rheumatology Vol. 8; no. 9; pp. 534 - 542
• Main Authors: Boilard, Eric, Blanco, Patrick, Nigrovic, Peter A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2012; Nature Publishing Group
• Subjects: 631/250/232/2051/1339; 692/420/2780; 692/699/1670/122/1613; 692/699/1670/498; Animals; Arthritis; Arthritis - blood; Arthritis - immunology; Arthritis - physiopathology; Autoimmunity - immunology; Blood clots; Blood platelets; Blood Platelets - immunology; Development and progression; Disease Models, Animal; Health aspects; Humans; Immunology; Leukocytes; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - physiopathology; Medicine; Medicine & Public Health; Mice; Neutrophils; Pathogenesis; Platelet Activation - immunology; review-article; Rheumatic diseases; Rheumatoid arthritis; Rheumatology; Synovial Fluid - immunology; Systemic lupus erythematosus; Canada; United States
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/nrrheum.2012.118

Platelets have an established function in haemostasis, but their role in the development of rheumatic disease is only now emerging. In this focused Review, Boilard and colleagues describe how platelets, and platelet-derived microparticles, contribute to the development of arthritis and systemic lupus erythematosus, highlighting the key advances in the literature and the future of this field. Nearly one trillion platelets circulate in the blood to monitor and preserve the integrity of the vasculature. However, haemostasis is not their only function. Platelets are also potent immune cells capable of a range of effector responses. Studies have shown that platelets can have unexpected roles in rheumatic diseases. In patients with rheumatoid arthritis (RA), IL-1-containing platelet-derived vesicles called microparticles are abundant in arthritic joint fluid. These microparticles can elicit production of inflammatory mediators from resident synovial fibroblasts, which have an integral role in the development of arthritis. Platelets also serve as a source of prostaglandins that contribute to synovial inflammation. Furthermore, serotonin released by platelets helps drive the persistent vascular permeability that characterizes the microvasculature of the inflamed synovium, an unexpected function for a cell that more typically serves as a guardian of vascular integrity. Beyond RA, platelet activation has been observed in systemic lupus erythematosus, mediated at least in part through the interaction of circulating immune complexes with platelet Fc receptors and by promotion of interferon release from plasmacytoid dendritic cells. These findings point to a distinct role for platelets in autoimmunity and support the possibility that platelets are an attractive target in rheumatic disease. Key Points Platelets patrol blood vessels to maintain haemostasis, but additionally have important roles in immunity and inflammation Upon activation, platelets shed submicron vesicles called microparticles; during inflammatory arthritis, these microparticles are abundant in synovial fluid and can exacerbate inflammation via proinflammatory mediators including IL-1 Prostaglandins are involved in inflammatory arthritis; prostaglandin I2 can be produced by platelets and fibroblast-like synoviocytes in a transcellular manner, a mechanism dependent on platelet-derived cyclooxygenase 1 Platelets promote vascular permeability in the arthritic joint; this process is mediated by serotonin that contributes to formation of endothelial gaps with submicron dimensions Evidence for platelet activation has been reported in systemic lupus erythematosus; this activation triggers the maturation of dendritic cells via platelet CD40L Platelet depletion and pharmacological blockade of platelet functions protects against lupus in mouse models of disease