Study on signal transduction pathway via integrins in autoimmune T cells

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It is now well recognized that integrins and their ligands are pivotal role in the first step of inflammation such as the adhesion between the leukocytes and the endothelial cells. Here, we showed data by a confocal image analyzer that the double stainig signals by anti-beta1 and anti-phosphotyrosine were observed in the perivascular and sublining areas in RA synovial cells, while it was not detected in OA,raising a possibility that the adhesive interaction not only mediates adhesion, but delivers the signals into the cell, contributing to maintain inflammation in RA synovium. To explore the mechanism, we examined the tyrosine phosphorylation of synovial cells in vitro culture system. The immunoblot for hospho-tyrosine demonstrated the five major proteins form the synovial cells in RA,while few faint bands were detected in OA.Since the pp125, among five major bands, was most prominent in RA synovial cells, we next examined whether pp125 is FAK or not.Immunoprecipitation with anti-pp125FAK has demonstrated that the band was pp125FAK itself and the tyrosine phosphorylation of pp125FAK was significantly elevated in RA synovial cells. Furthermore, confocal laser microscopy showed that the signals by anti-phosphotyrosine and anti-pp125FAK were abundantly detected in macrophage-like synovial cells.