{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:31:46Z","timestamp":1791246706767,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,2,29]],"date-time":"2008-02-29T00:00:00Z","timestamp":1204243200000},"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":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the functional roles of plasmin in a murine model of <jats:italic>Staphylococcus aureus<\/jats:italic>\u2013induced bacterial arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bacterial arthritis was induced in plasminogen\u2010deficient (Plg<jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type (Plg<jats:sup>+\/+<\/jats:sup>) littermates by local injection of 1 \u00d7 10<jats:sup>6<\/jats:sup> colony\u2010forming units of <jats:italic>S aureus<\/jats:italic> into the knee joints. Human plasminogen was administered to Plg<jats:sup>\u2212\/\u2212<\/jats:sup> mice on days 0\u20137 or days 7\u201314. Antibiotic treatment was administered to Plg<jats:sup>\u2212\/\u2212<\/jats:sup> mice on days 7\u201314. Bacteria counts and histologic, immunohistochemical, and Western blot analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In Plg<jats:sup>+\/+<\/jats:sup> mice, <jats:italic>S aureus<\/jats:italic> counts had declined within 2 days, and by day 28 the bacteria had been completely eliminated. However, <jats:italic>S aureus<\/jats:italic> was still detectable in all injected joints from Plg<jats:sup>\u2212\/\u2212<\/jats:sup> mice, and bacteria counts were 27 times higher than the amount injected on day 0. The extent of macrophage and neutrophil recruitment to the infected joints was comparable for Plg<jats:sup>+\/+<\/jats:sup> and Plg<jats:sup>\u2212\/\u2212<\/jats:sup> mice on days 1, 7, and 14. The activation of these inflammatory cells appeared to be impaired in Plg<jats:sup>\u2212\/\u2212<\/jats:sup> mice, however. Treatment of Plg<jats:sup>\u2212\/\u2212<\/jats:sup> mice with antibiotic (cloxacillin) resulted in successful killing of the bacteria, but the necrotic tissue remained in the infected joints. When human plasminogen was given intravenously to Plg<jats:sup>\u2212\/\u2212<\/jats:sup> mice daily for 7 days, bacterial clearance was greatly improved as compared with their untreated counterparts, and the amount of necrotic tissue in the joint cavity was dramatically reduced. The expression of interleukin 6 (IL\u20106) and IL\u201010 was higher in Plg<jats:sup>+\/+<\/jats:sup> mice than in Plg<jats:sup>\u2212\/\u2212<\/jats:sup> mice during bacterial arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that plasmin plays a pluripotent role in protecting against <jats:italic>S aureus<\/jats:italic>\u2013induced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23263","type":"journal-article","created":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T00:49:18Z","timestamp":1204332558000},"page":"764-772","source":"Crossref","is-referenced-by-count":35,"title":["Protective effects of plasmin(ogen) in a mouse model of <i>Staphylococcus aureus<\/i>\u2013induced 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