Eda‐containing fibronectin is synthesized from rheumatoid synovial fibroblast‐like cells

OBJECTIVE: To identify the cells that synthesize EDA-containing fibronectin (FN) and examine the role of EDA+FN in the pathogenesis of rheumatoid joint lesions. METHODS: Localization of EDA+FN and c-Fos protein in rheumatoid joints was studied immunohistochemically by utilizing antibodies for EDA+FN and c-Fos. Expression of EDA+FN was studied by immunoelectron microscopy and in situ hybridization. The amount of EDA+FN was measured by enzyme-linked immunosorbent assay. RESULTS: EDA+FN was specifically localized in the synovial lining layer of synovium with active rheumatoid arthritis (RA) (n = 17), but not in that with osteoarthritis (n = 4) or with inactive fibrous RA (n = 2). EDA+FN messenger RNA was localized in the synovial lining layer. EDA+FN was immunoelectron microscopically localized in the synovial lining fibroblast-like (type B) cells. EDA+FN was also detected at the cartilage-pannus junction and on the surface of RA cartilage. Double staining showed that EDA+FN colocalized with c-Fos protein in the rheumatoid synovial lining layer. Quantification of EDA+FN showed that it was highly concentrated in rheumatoid synovial fluids. CONCLUSION: EDA+FN is synthesized by the synovial lining fibroblast-like (type B) cells in situ in rheumatoid synovium, and appears to be expressed in association with activated or transformed states of synovium.