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.
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.
Lazarovits
A I
AI
John P. Robarts Research Institute, University Hospital, London, Ontario, Canada.
Karsh
J
J
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000032:analysis*; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D017469:Receptors, Fibronectin / Q000032:analysis*; D013582:Synovial Fluid / Q000737:chemistry*; D013583:Synovial Membrane / Q000737:chemistry*; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D016023:Integrins; D017469:Receptors, Fibronectin; D019010:Vascular Cell Adhesion Molecule-1