THE ROLE OF ADHESION MOLECULES IN THE CHRONICITY AND JOINT DESTRUCTION OF ARTHRITEDES

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We studied the staining pattern of a group of adhesion molecules in the lining layr and lymphocytic infiltrates of the rheumatoid synovial membrane, using monoclonal antibodies sgainst LFA-1, VLA-4, VLA-5, ELAM-1 and ICAM-1. The cells of the lining layr were strongly ICAM-1 positive and VLA-5 positive, suggesting 1) that ICAM-1 may function to facilitate the adhesion of ICAM-1 bearing type A cells to type B lining cells and 2) that the lining cells may utilize VLA-5 for anchorage to fibronectin at surface of the synovial membrane. In the lymphocyte-rich and transitional areas, the endothelial cells of the venules were both ELAM-1 and ICAM-1 positive. ICAM-1 staining was weak in lymphoid aggregate, but strong in the transitional areas, indcating a paucity of ICAM-1 bearing cells in the lymphocyte-rich areas. On the other hand, LFA-1 staining was very strong in the lymphoid aggregates. This suggested that the large numbers of T4 cells present in the lymphocyte-rich areas are sufficiently activated to express substatial levels of LFA-1, and also that the LFA-1 molecules is an important receptor for emigration from venules. Furthermore to investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohistochemical studies were carried out. ICAM-1 positive macrophages and fibroblasts were often found to be contact with lymphoid cells, suggesting that a cellular immune reaction occurs in the formation of the pannus. The VLA-5 molecules was found in a pericellular and interterritorial matrix distribution, 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 b1 integrin may be necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to indrease attachment.