Tyrosine phosphorylation in the synovium of patients with rheumatoid arthritis and rats with experimental arthritis.

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Synovial tissues from patients with rheumatoid arthritis (RA) are characterized by tumor-like proliferation (diffuse and nodular mononuclear cell infiltration and hyperplasia of the stromal connective tissues), which induces the destruction of bone and cartilage. In the previous study, we demonstrated that fibroblast growth factor (FGF)-1, platelet-derived growth factor (PDGF) and PDGF receptors (α, β) were intensely immunolocalized in the synovium of patients with RA higher than osteoarthritis (OA). The receptors for FGF and PDGF are tyrosine kinases. In this study, we examined the expression of tyrosine phosphorylated proteins (PT) in arthritic joints of patients with RA and rats with streptococcal cell wall (SCW)-and adjuvant-induced arthritis. PT was intensely immunostained in synovial lining cell layer, fibroblast-like cells, vascular endothelium and inflammatory mononuclear cells from RA patients in contrast to synovia from OA or normal subjects. Moreover, PT was expressed in synovium, cartilage and skin epidermis of SCW-induced arthritis in Lewis rats (LEW/N). PT expression was detected at day 4 after adjuvantinjection in Lewis rats without clinical apparent arthritis. PT expression was not sustained in athymic Lewis rats (LEW. rnu/rnu) after injection of SCW or adjuvant. This observation demonstrates that persistent expression of PT, as well as chronic arthritis, requires an intact T lymphocyte-dependent immune system. Staining with anti-PT antibody was absent in relatively arthritis-resistant Fisher rats (F 344/N) after injection of SCW or adjuvant. These results suggested that FGF-1 and PDGF-A and B-like factors were active in vivo in inflammatory joints and promoted the tumor-like behavior of rheumatoid synovium throughtyrosine phosphorylation.
日本臨床免疫学会の論文

Tyrosine phosphorylation in the synovium of patients with rheumatoid arthritis and rats with experimental arthritis.

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