Alternatively spliced CS-1 fibronectin isoform and its receptor VLA-4 in rheumatoid arthritis synovium.

Abstract

Extracellular matrix components and cell adhesion molecules play a role in the pathogenesis of rheumatoid arthritis (RA). Interaction between the integrin very late antigen-4 (VLA-4) and the connecting segment-1 (CS-1) fibronectin (FN) isoform may contribute to lymphocyte interaction in RA synovium. We examined both mRNA and protein expression of CS-1 FN in inflamed synovium, and VLA-4 expression in synovial tissue and on cultured fibroblast-like synoviocytes from patients with RA. Snap frozen synovial tissue specimens of 10 patients with RA and 4 patients with osteoarthritis were examined for expression of CS-1 FN mRNA and protein by in situ hybridization and immunohistochemistry. VLA-4 expression of synovial fibroblasts and in synovial tissue was evaluated by flow cytometry and immunohistochemistry. 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-1 FN mRNA were CD68 negative. VLA-4 was found in RA synovial fibroblasts, sublining mononuclear cells, and lymphoid aggregates. 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.