The role of VCAM-1 molecule in the pathogenesis of rheumatoid synovitis.

The present review focuses on the possible role of VCAM-1 expression on synovial fibroblast-like cells in the synovial lesion of rheumatoid arthritis (RA). The VCAM-1 expressing cells were mainly present in the synovial lining layer. The VCAM-1 expressing fibroblast-like cells also showed activity of uridine diphosphoglucose dehydrogenase, indicating that they are activated fibroblasts. VCAM-1 expressing T cells were also found in RA synovial fluids, where T lymphocytes show upregulation of alpha 4 beta 1 expression, and these T lymphocytes are able to bind to VCAM-1 in solid phase. Further experiments excluded the production of VCAM-1 protein in synovial fluid T lymphocytes and supported the idea that the soluble VCAM-1 was bound to the surface of synovial fluid T lymphocytes. We next planned to examine the effect of soluble VCAM-1 on T cell functions, by using recombinant soluble VCAM-1. The recombinant soluble VCAM-1 rendered synovial or peripheral T cells anergic to various stimuli. These findings imply that recombinant soluble VCAM-1 might be useful as a therapeutic tool to prevent abnormal immune response, since it binds to activated T lymphocytes with upregulation of alpha 4 beta 1, but not to resting T lymphocytes, and soluble VCAM-1 bound T lymphocytes become anergic.