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 x 10(6) 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.


CONCLUSIONS
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.
Guo
Yongzhi
Y
Umeå University, Umeå, Sweden.
Li
Jinan
J
Hagström
Elin
E
Ny
Tor
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001170:Arthritis, Infectious / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D003023:Cloxacillin / Q000627:therapeutic use; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010958:Plasminogen / Q000378:metabolism* / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D013211:Staphylococcus aureus
D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D016753:Interleukin-10; D010958:Plasminogen; D005341:Fibrinolysin; D003023:Cloxacillin