title: An immunohistochemical and immunoelectron microscopic study of adhesion molecules in synovial pannus formation in rheumatoid arthritis.
abstract: To investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohistochemical and immunoelectron microscopic studies with monoclonal antibodies against the adhesion molecules, CD54 (ICAM-1), CD11a (LFA-1), CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), Cdw49d (VLA-4) and CDw49e (VLA-5), were carried out to determine the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction. Treatment with anti-ICAM-1 resulted in membrane staining of most of the macrophages and fibroblasts infiltrating the synovial tissue and bordering and pannus-cartilage junction, suggesting the possibility that ICAM-1 may function to facilitate the adhesion of synovial type A cells bearing ICAM-1 to type B cells of the pannus. ICAM-1 positive macrophages and fibroblasts were often found to be in contact with lymphoid cells, suggesting also that a cellular immune reaction occurs in the formation of the pannus. In addition, VLA-3, VLA-4 and, particularly, VLA-5 were the predominant beta 1 integrins expressed by rheumatoid synovial pannus. Sine these three integrins all function as fibronectin receptors, it is possible that the fibronectin-rich environment of the rheumatoid cartilage surface effectively traps pannus cells expressing high levels of these molecules. The VLA-5 molecule was found in a pericellular and interterritorial matrix distribution in the present study, strongly suggesting that a receptor-ligand interaction between VLA-5 and cartilage matrix may occur at the early stage of pannus formation. Furthermore, an increase in beta 1 integrin may be necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to increased attachment.
authors.affiliation: Faculty of Health Science, Kobe University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishikawa
authors.forename: S
authors.initials: S
authors.lastname: Hirata
authors.forename: Y
authors.initials: Y
authors.lastname: Andoh
authors.forename: H
authors.initials: H
authors.lastname: Kubo
authors.forename: N
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nishibayashi
authors.forename: K
authors.initials: K
authors.lastname: Mizuno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D013583:Synovial Membrane / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000911:Antibodies, Monoclonal; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1