Eric Boilard, PhD, David Lee, MD PhD, and colleagues in the Rheumatology, Immunology and Allergy Department at BWH in collaboration with a team of researchers from the University of Cambridge in Britain, have found that platelets- small irregularly shaped anuclear cells better known for their aid in blood clotting- and platelet microparticles, play a role in rheumatoid arthritis by releasing small platelet vesicles called microparticles. These findings appear in the Jan. 29, issue of Science.  
 
Prompted by a growing literature regarding the pro-inflammatory capacity of platelets, the researchers investigated whether platelets participated in another common inflammatory condition: inflammatory arthritis. They identified platelet microparticles in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis. Platelet microparticles were pro-inflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin 1. In addition, using both pharmacologic and genetic approaches, the researchers 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.
 
Current strategies to treat arthritis involve a blockade of immune cell function and are therefore immunosuppressive. The authors suggest these findings can open the way to new non-immunosuppressive therapeutics targeting platelet activation and microparticles release in arthritis, and most likely in other inflammatory disorders where platelets were also overlooked. The authors also suggest that platelet involvement in inflammatory arthritis likely extends beyond the mechanisms identified so far, thus extensive further research is planned.

The National Institutes of Health, the Cogan Family Foundation, the Arthritis Foundation and the British Heart Foundation and Medical Research Council funded this research.

Figure caption: Proposed pathway for GPVI-dependent participation of platelets in arthritis via microparticles. GPVI-expressing platelets activated by collagen produce copious amounts of IL-1-rich microparticles (MPs) (left panel and inset). The precise anatomic location of platelet activation, and the route by which microparticles enter the joint (dashed red line with arrows), remain unknown. Platelet MPs (~0.2 -1 µm in diameter), detectable at high levels in inflammatory synovial fluid, interact with tissue cells including fibroblast-like synoviocytes (FLS) and synovial fluid leukocytes (right panel).  This interaction elicits further inflammatory effector functions from target cells thereby amplifying synovitis.  In the case of FLS, platelet MPs promote elaboration of IL-8 and other mediators that are capable of leukocyte chemoattraction to the joint (right panel). Platelet microparticles attached to neutrophils, as found in diseased synovial fluid, may also stimulate neutrophil effector functions, although this remains to be established (question mark right panel). Illustration by Steve Moskowitz, Advanced Medical Graphics. 

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Source: Brigham and Women’s Hospital (BWH)