Platelets play a role in rheumatoid arthritis by releasing small platelet vesicles called microparticles.
Online PR News – 10-February-2010 – – 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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Brigham and Women's Hospital (BWH) is a 777-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. In July of 2008, the hospital opened the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 860 physician-investigators and renowned biomedical scientists and faculty supported by more than $416 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit http://www.brighamandwomens.org/