Differential expression in rheumatoid synovium and synovial fluid of alpha 4 beta 7 integrin. A novel receptor for fibronectin and vascular cell adhesion molecule-1.

Abstract

T lymphocyte adhesion to vascular endothelium plays an important role in the immunopathogenesis of rheumatoid arthritis. The migration of T lymphocytes into the synovium is mediated by a variety of adhesion molecules, notably the integrins. We have prepared Act I, a murine mAb that identifies a novel integrin termed alpha 4 beta 7. The natural ligands for alpha 4 beta 7 are vascular cell adhesion molecule-1 and fibronectin; both molecules are up-regulated in the rheumatoid synovium. We investigated the expression of alpha 4 beta 7 in the three compartments of rheumatoid arthritis, the peripheral blood, synovial fluid, and synovial membrane, utilizing the FACS and immunoperoxidase microscopy of frozen tissues. The results of our experiments show a striking differential expression of alpha 4 beta 7 integrin in rheumatoid arthritis. Sixty-two percent of synovial membrane T cells expressed high density alpha 4 beta 7, in contrast to only 4.7% of synovial fluid and 9.1% of PBL. These data suggest that the expression of alpha 4 beta 7 integrin may provide a mechanism whereby certain T cells adhere to rheumatoid synovium while others remain in the synovial fluid. The augmented expression of alpha 4 beta 7 in the synovial membrane T cells may contribute to the development and perpetuation of rheumatoid arthritis.