AN IMMUNOHISTOCHEMICAL AND IMMUNOELECTRON MICROSCOPIC STUDY OF ADHESION MOLECULES IN SYNOVIAL PANNUS FORMATION IN RHEUMATOID-ARTHRITIS

To investigate the mechanism of synovial pannus formation in rheumatoi d arthritis, immunohistochemical and immunoelectron microscopic studie s with monoclonal antibodies against the adhesion molecules, CD54 (ICA M-1), CD11a(LFA-1), CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), Cd w49d (VLA-4) and CDw49e (VLA-5), were carried out to determine the pat tern of distribution of these molecules at the rheumatoid synovial car tilage junction. Treatment with anti-ICAM-1 resulted in membrane stain ing of most of the macrophages and fibroblasts infiltrating the synovi al tissue and bordering the pannus-cartilage junction, suggesting the possibility that ICAM-1 may function to facilitate the adhesion of syn ovial 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 conta ct with lymphoid cells, suggesting also that a cellular immune reactio n 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. Since these three integrins all functio n as fibronectin receptors, it is possible that the fibronectin-rich e nvironment of the rheumatoid cartilage surface effectively traps pannu s cells expressing high levels of these molecules. The VLA-5 molecule was found in a pericellular and interterritorial matrix distribution i n the present study, strongly suggesting that a receptor-ligand intera ction between VLA-5 and cartilage matrix may occur at the early stage of pannus formation. Furthermore, an increase in beta 1 integrin may b e necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to increased attachment.