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.