EFFECT OF THE NEPHRITOGENIC AUTOANTIBODY OF HEYMANNS NEPHRITIS ON PLASMINOGEN-BINDING TO GP330 AND ACTIVATION BY UROKINASE

Previous results have shown that the autoantibody eluted from the glom eruli of rats with active Heymann nephritis contain a population of an tibodies not only to the putative autoantigen of the disease, gp330, b ut also to plasminogen. Since gp330 has been shown to serve as a recep tor for plasminogen, we have analyzed the effects of autoantibody on p lasminogen-binding to gp330 and activation of plasminogen to plasmin b y urokinase. Autoantibody does not inhibit the binding of plasminogen to gp330. The binding of autoantibody to plasminogen was shown to be v ery specific for the compact conformation of glu-plasminogen. The chan ge in the conformation of plasminogen when its lysine-binding sites ar e occupied or after conversion to plasmin results in a significant dec rease in autoantibody-binding. The most significant effect of autoanti body on this system is the inhibition of plasminogen activation to pla smin by urokinase. The binding of autoantibody to plasminogen acts as a competitive inhibitor of the reaction by apparently blocking access of urokinase to plasminogen's activation site. These results indicate that autoantibody obtained from the immune deposits in the glomeruli o f rats with active Heymann nephritis does not inhibit the binding of p lasminogen to gp330 but does significantly alter the urokinase catalyz ed activation of plasminogen to plasmin.