Role of selectins in experimental Staphylococcus aureus-induced arthritis.
The selectin family of adhesion molecules mediates the initial attachment of leukocytes to venular endothelial cells at sites of tissue injury and inflammation. To assess the role of selectin family in Staphylococcus aureus-triggered septic arthritis, we used several approaches. First, treatment with fucoidin, a carbohydrate molecule capable of binding to and blocking selectin functions, was used. In addition, we used P-selectin gene-targeted mice as well as mice pretreated with monoclonal antibody blocking L-selectin function. The P-selectin-deficient and fucoidin-treated animals initially exhibited a less severe septic arthritis both clinically and histopathologically. In the later stages of the disease no significant differences with respect to arthritis were evident. Pretreatment with L-selectin blocking antibody did not influence the severity of arthritis. High numbers of staphylococci were recovered from the kidneys of selectin-deficient mice, indicating a less efficient clearance of bacteria. Our results demonstrate a dual role for selectins in S. aureus-induced arthritis: on the one hand, blockade of these selectins leads to less severe arthritic lesions in the initial stage of the disease; on the other, delayed recruitment of phagocytes decreases the clearance of bacteria.
Verdrengh
M
M
Department of Rheumatology, University of Göteborg, Sweden. margareta.verdrengh@immuno.gu.se
Erlandsson-Harris
H
H
Tarkowski
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000276:immunology; D001170:Arthritis, Infectious / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007596:Joints / Q000473:pathology; D019041:L-Selectin / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011134:Polysaccharides / Q000008:administration & dosage / Q000276:immunology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019007:P-Selectin; D011134:Polysaccharides; D019041:L-Selectin; C007789:fucoidan