CYTOTOXICITY TO ENDOTHELIAL-CELLS BY SERA FROM AGED MRL LPR/LPR MICE IS ASSOCIATED WITH AUTOIMMUNITY TO CELL-SURFACE HEPARAN-SULFATE/

Vasculitis is an common clinical feature of systemic lupus erythematos us (SLE) in humans and in animal models of this disease. Humoral autoi mmunity against endothelial cells has been previously demonstrated in SLE and other autoimmune disorders, but the precise cell surface antig enic targets involved in the initiation and progression of vascular in jury are still essentially unknown. In the current studies, we demonst rate the presence of autoantibodies in the sera of MRL/lpr/lpr mice wh ich bind endothelial cell surface antigens by ELISA and also cause com plement-dependent cytotoxicity of these cells. These MRL/lpr/lpr sera induced complement-dependent cleavage and release of (SO4)-S-35-labele d material containing primarily cell surface heparan sulfate proteogly cans from these cells, and react with heparin (a glycosaminoglycan rel ated to heparan sulfate) by ELISA and liquid-phase competitive inhibit ion ELISA. These data indicate that antiendothelial cell autoantibodie s present in autoimmune MRL/lpr/lpr mice are directed at least in part against cell surface heparan sulfate proteoglycans. Autoantibodies to cell surface heparan endothelial cell injury in these animals through complement-dependent, autoimmune mechanisms. (C) 1995 Academic Press, Inc.