Acceleration and increased severity of collagen-induced arthritis in P-selectin mutant mice

P-selectin plays an important role in leukocyte adherence to microvascular endothelium and is expressed in synovial tissue horn patients with rheumato id arthritis (RA), However, the contribution of P-selectin to the initiatio n and chronicity of joint inflammation is not well understood. In these stu dies, collagen-induced arthritis (CIA) was induced in P-selectin mutant (-/ -) mice Co explore the role of P-selectin in the development of joint infla mmation Surprisingly, CIA onset was accelerated and severity was increased in P-selectin mutant mice, compared with wild-type mice (+/+), Increased le vels of anti-type II. collagen IgG were detected in both nonarthritic and a rthritic P-selectin mutant mice from days 14-91, In addition, splenocytes i solated from immunized and nonimmumized P-selectin mutant mice produced sig nificantly less IL-2 and IL-4, but significantly higher levels of IL-IO and IL-5 than splenocytes from wild-type mice. These observations show that P- selectin-mediated leukocyte rolling is not. required for the development of murine CIA and that P-selectin expression exerts a controlling effect on t he development of Ag-driven in inflammatory joint disease, possibly by medi ating the recruitment and/or trafficking of specific leukocyte subtypes int o lymphoid tissue or inflammatory foci.