期刊
EMBO MOLECULAR MEDICINE
卷 5, 期 2, 页码 235-249出版社
WILEY-BLACKWELL
DOI: 10.1002/emmm.201201846
关键词
arthritis; autoantigens; immune complexes; microparticles; platelets
资金
- Canadian Arthritis Network
- NIH [P01 AI065858]
- Arthritis Foundation Investigator Award
- Cogan Family Foundation
- Orthopaedic Research and Education Foundation
- British Heart Foundation [RG/09/003/27122] Funding Source: researchfish
Immunoglobulins, antigens and complement can assemble to form immune complexes (IC). ICs can be detrimental as they propagate inflammation in autoimmune diseases. Like ICs, submicron extracellular vesicles termed microparticles (MP) are present in the synovial fluid from patients affected with autoimmune arthritis. We examined MPs in rheumatoid arthritis (RA) using high sensitivity flow cytometry and electron microscopy. We find that the MPs in RA synovial fluid are highly heterogeneous in size. The observed larger MPs were in fact MP-containing ICs (mpICs) and account for the majority of the detectable ICs. These mpICs frequently express the integrin CD41, consistent with platelet origin. Despite expression of the Fc receptor FcRIIa by platelet-derived MPs, we find that the mpICs form independently of this receptor. Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs. Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene production by neutrophils. Taken together, our data suggest a unique role for platelet MPs as autoantigen-expressing elements capable of perpetuating formation of inflammatory ICs.
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