INCREASED SYNOVIAL EXPRESSION OF TRANSFORMING GROWTH-FACTOR (TGF)-BETA RECEPTOR ENDOGLIN AND TGF-BETA-1 IN RHEUMATOID-ARTHRITIS - POSSIBLE INTERACTIONS IN THE PATHOGENESIS OF THE DISEASE

The ingress of inflammatory cells into the rheumatoid (RA) synovial ti ssue (ST) plays a role in the pathogenesis of this disease. Transformi ng growth factor beta (TGF-beta) may play a role in this process. We h ave investigated the distribution of endoglin, a newly described recep tor for TGF-beta 1 and -beta 3, in RA compared to osteoarthritis (OA) or normal ST. Immunohistochemical analysis was carried out using an an ti-TGP-beta 1 monoclonal antibody (mAb) as well as 10 mAbs raised agai nst various epitopes of endoglin. This study was performed on ST from 10 patients with RA, 10 with OA, and 4 normal individuals. TGF-beta 1 expression was significantly up-regulated on RA compared to OA and nor mal ST lining cells, interstitial macrophages, and endothelial cells ( P < 0.05). All anti-endoglin mAbs uniformly reacted with endothelial c ells in RA, OA, and normal STs. However, 3 out of 10 anti-endoglin mAb s reacted with significantly more RA versus normal ST lining cells (P < 0.05), as well as RA compared to OA and normal macrophages (P < 0.05 ). There was a positive correlation between TGF-beta 1 and endoglin re activity on the synovial lining layer and subsynovial macrophages (P < 0.05). These results indicate that TGF-beta 1 and certain epitopes of endoglin, a TGP-beta 1 and -beta 3 receptor, are up-regulated on myel oid elements in RA compared to normal ST. Endoglin is also present on ST endothelia, and its expression may also be increased on OA compared to normal ST lining cells. These findings implicate endoglin in the p athogenesis Of RA. (C) 1995 Academic Press, Inc.