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Platelets: active players in the pathogenesis of arthritis and SLE

Abstract

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

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Figure 1: The multiple facets of platelets.
Figure 2: Mechanisms by which platelets can enhance inflammation during arthritis.
Figure 3: Platelet-dependent vascular leakage in the arthritic joint.
Figure 4: Different activation processes involving platelets in SLE.

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E. Boilard and P. Blanco reasearched data for the article. E. Boilard and P. Nigrovic made equal contributions to discussion of content and reviewing and/or editing the manuscript before submission. All authors wrote the article.

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Correspondence to Eric Boilard.

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Boilard, E., Blanco, P. & Nigrovic, P. Platelets: active players in the pathogenesis of arthritis and SLE. Nat Rev Rheumatol 8, 534–542 (2012). https://doi.org/10.1038/nrrheum.2012.118

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