Acceleration and Increased Severity of Collagen-Induced Arthritis in P-Selectin Mutant Mice
| Autor: | Daniel C. Bullard, James M. Mobley, James M. Justen, Laurel M. Sly, John G. Chosay, Colin J. Dunn, J. Russell Lindsey, Arthur L. Beaudet, Nigel D. Staite |
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| Rok vydání: | 1999 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 163:2844-2849 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | P-selectin plays an important role in leukocyte adherence to microvascular endothelium and is expressed in synovial tissue from patients with rheumatoid arthritis (RA). However, the contribution of P-selectin to the initiation and chronicity of joint inflammation is not well understood. In these studies, collagen-induced arthritis (CIA) was induced in P-selectin mutant (−/−) mice to explore the role of P-selectin in the development of joint inflammation. Surprisingly, CIA onset was accelerated and severity was increased in P-selectin mutant mice, compared with wild-type mice (+/+). Increased levels of anti-type II collagen IgG were detected in both nonarthritic and arthritic P-selectin mutant mice from days 14–91. In addition, splenocytes isolated from immunized and nonimmunized P-selectin mutant mice produced significantly less IL-2 and IL-4, but significantly higher levels of IL-10 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 the development of Ag-driven inflammatory joint disease, possibly by mediating the recruitment and/or trafficking of specific leukocyte subtypes into lymphoid tissue or inflammatory foci. |
| Databáze: | OpenAIRE |
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