{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:22:02Z","timestamp":1789849322823,"version":"4.0.1"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2004,8,5]],"date-time":"2004-08-05T00:00:00Z","timestamp":1091664000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Monosodium urate monohydrate (MSU) crystals promote gouty inflammation that is critically mediated by neutrophil recruitment and activation. Interleukin\u20108 (IL\u20108) and closely related chemokines are major neutrophil chemotaxins in experimental gout. But MSU crystals also activate the classical and alternative pathways of complement, and MSU crystals directly cleave C5 on the crystal surface. Unlike IL\u20108, the roles in acute gout of individual complement\u2010derived peptides and of the terminal C5b\u20139 complement components that comprise the membrane attack complex (MAC) are unclear. Hence, we studied rabbits deficient in the MAC component C6 to determine if MAC mediated urate crystal\u2013induced arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We injected C6\u2010deficient and C6\u2010sufficient rabbit knee joints with 10 mg of pyrogen\u2010free urate crystals and analyzed IL\u20108 levels, leukocyte influx, and joint inflammation 24 hours later.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a significant decrease (&gt;60%) in swelling in MSU crystal\u2013injected knees of C6\u2010deficient animals as compared with C6\u2010sufficient animals (<jats:italic>P<\/jats:italic> &lt; 0.05). An attenuated rise in MSU crystal\u2013induced joint effusion levels of IL\u20108 also was observed, which was concordant with diminished numbers of neutrophils (<jats:italic>P<\/jats:italic> &lt; 0.05) but not monocytes in MSU crystal\u2013induced knee synovial fluid from C6\u2010deficient animals. Synovial tissue analysis confirmed mononuclear leukocyte infiltration in response to MSU crystal injection in all animals, but substantial neutrophil infiltration only in C6\u2010sufficient animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MAC activation appears to play a major role in intraarticular IL\u20108 generation and in neutrophil recruitment in experimental acute gouty arthritis of the rabbit knee. C6 and MAC activation may represent novel therapeutic targets for suppression of neutrophil\u2010mediated joint inflammation in gout.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20386","type":"journal-article","created":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T18:17:34Z","timestamp":1092075454000},"page":"2633-2639","source":"Crossref","is-referenced-by-count":70,"title":["Central role of complement membrane attack complex in monosodium urate crystal\u2013induced neutrophilic rabbit knee synovitis"],"prefix":"10.1002","volume":"50","author":[{"given":"Nicole","family":"Tramontini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Huber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Liu\u2010Bryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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