Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus-induced arthritis

• Objective: To assess the functional roles of plasmin in a murine model of Staphylococcus aureus-induced bacterial arthritis. Methods: Bacterial arthritis was induced in plasminogen-deficient (Plg-/-) and wild-type (Plg+/+) littermates by local injection of 1 × 106 colony-forming units of S aureus into the knee joints. Human plasminogen was administered to Plg-/- mice on days 0-7 or days 7-14. Antibiotic treatment was administered to Plg-/- mice on days 7-14. Bacteria counts and histologic, immunohistochemical, and Western blot analyses were performed. Results: In Plg+/+ mice, S aureus counts had declined within 2 days, and by day 28 the bacteria had been completely eliminated. However, S aureus was still detectable in all injected joints from Plg-/- 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+/+ and Plg-/- mice on days 1, 7, and 14. The activation of these inflammatory cells appeared to be impaired in Plg-/- mice, however. Treatment of Plg-/- 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-/- 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-6) and IL-10 was higher in Plg+/+ mice than in Plg-/- mice during bacterial arthritis. Conclusion: Our findings indicate that plasmin plays a pluripotent role in protecting against S aureus-induced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression.

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