EFFECTS OF THROMBOSPONDIN-1 ON DISEASE COURSE AND ANGIOGENESIS IN RATADJUVANT-INDUCED ARTHRITIS

Leukocyte extravasation into the synovium is important in rheumatoid a rthritis (RA). Thrombospondin (TSP)-1 mediates cell adhesion and migra tion and inhibits angiogenesis, and it has been implicated in RA, Howe ver, little information is available on the role of TSP-1 in arthritis -associated inflammation and neovascularization. Therefore, we analyze d the effects of TSP-I in adjuvant-induced arthritis (ATA), a rat mode l for RA. Hydron pellets containing TSP-1 were implanted in one ankle of AIA rats post-adjuvant injection, while the contralateral ankle rec eived sham implants. Body weight loss and joint swelling were determin ed in comparison to nonimplanted AIA controls. In addition, synovial v essel counts were obtained in TSP-1-versus sham-implanted ankles of th e same rat. The implantation of TSP-1 pellets into one ankle resulted in an enhancement of swelling in both ankles. Furthermore, TSP-1 exhib ited a biphasic modulatory effect on synovial vessel counts (P < 0.05) . In conclusion, TSP-1 implanted into one ankle of AIA rats may augmen t the severity of the disease. One possible explanation, among others, for the modulating effect of TSP-1 on inflammation may be its effect on arthritis-related angiogenesis. (C) 1998 Academic Press.