{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:25:52Z","timestamp":1791257152532,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,1,28]],"date-time":"2011-01-28T00:00:00Z","timestamp":1296172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Rheumatoid arthritis culminates in joint destruction that, in mouse models of disease, is supported by innate immune molecules, including Fc\u03b3 receptors (Fc\u03b3R) and complement. However, these findings may not be predictive of the outcome in humans, given the structural differences between murine and human activating Fc\u03b3R on neutrophils, a prominent component of joint exudates. The aim of this study was to examine the role of human neutrophil Fc\u03b3RIIa in the development of arthritis and probe the underlying mechanism by which Fc\u03b3RIIa initiates disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>K\/BxN mouse serum transfer\u2013induced arthritis was examined in mice expressing human Fc\u03b3RIIa on neutrophils but lacking their own activating Fc\u03b3R (\u03b3\u2010chain\u2013deficient mice). The role of mast cells, complement (C3 and C5a), and CD18 integrins in Fc\u03b3RIIa\u2010initiated disease was examined using cell reconstitution approaches, inhibitors, and functional blocking antibodies, respectively. Crosstalk between the complement receptor C5aR and Fc\u03b3RIIa on neutrophils was evaluated in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of human Fc\u03b3RIIa on neutrophils was sufficient to restore susceptibility to K\/BxN serum\u2013induced neutrophil recruitment, synovitis, and bone destruction in \u03b3\u2010chain\u2013deficient mice. Joint inflammation was robust and proceeded even in the absence of mast cells and vascular permeability, features shown to contribute to disease in wild\u2010type mice. Neutrophil recruitment was dependent on the presence of a CD18 integrin, lymphocyte function\u2013associated antigen 1, and C5aR. In addition, C5aR significantly enhanced Fc\u03b3RIIa\u2010mediated phagocytosis and oxidative burst in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Human and murine activating Fc\u03b3R on neutrophils are not functionally equivalent, and in humans, they may play a primary role in arthritis. Crosstalk between neutrophil C5aR and Fc\u03b3RIIa is essential for disease progression, thus highlighting a new aspect of complement during the effector phase of inflammatory arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30141","type":"journal-article","created":{"date-parts":[[2010,11,12]],"date-time":"2010-11-12T17:54:25Z","timestamp":1289584465000},"page":"467-478","source":"Crossref","is-referenced-by-count":69,"title":["Regulation of human neutrophil Fc\u03b3 receptor IIa by C5a receptor promotes inflammatory arthritis in mice"],"prefix":"10.1002","volume":"63","author":[{"given":"Naotake","family":"Tsuboi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Cullere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Mekala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Hazen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"K\u00f6hl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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