ALTERNATIVELY SPLICED CS-1 FIBRONECTIN ISOFORM AND ITS RECEPTOR VLA-4IN RHEUMATOID-ARTHRITIS SYNOVIUM

Objective. Extracellular matrix components and cell adhesion molecules play a role in the pathogenesis of rheumatoid arthritis (RA), Interac tion between the integrin very late antigen-4 (VLA-4) and the connecti ng segment-1 (CS-1) fibronectin (FN) isoform may contribute to lymphoc yte interaction in RA synovium. We examined both mRNA and protein expr ession of CS-I FN in inflamed synovium, and VLA-4 expression in synovi al ! tissue and on cultured fibroblast-like synoviocytes from patients with RA. Methods, Snap frozen synovial tissue specimens of 10 patient s with RA and 4 patients with osteoarthritis were examined for express ion of CS-I FN mRNA and protein by ill situ hybridization and immunohi stochemistry. VLA-4 expression of synovial fibroblasts and in synovial tissue was evaluated by flow cytometry and immunohistochemistry. Resu lts, CS-1 FN mRNA was detected in RA lining layer synoviocytes, around terminal vessels, and in endothelial cells. Double labeling revealed that most lining synoviocytes expressing CS-I FN mRNA were CD68 negati ve, VLA-4 was found in RA synovial fibroblasts, sublining mononuclear cells, and lymphoid aggregates. Conclusion. Our findings suggest that expression of CS-1 FN may partially correlate with cell proliferation in the RA lining layer. VLA-4 was found in RA synovial lining, as well as on cultured synovial fibroblasts, Thus, VLA-4/CS-1 FN interaction may facilitate lymphocyte interaction and synovial proliferation in RA .