Effect of the nephritogenic autoantibody of Heymann's nephritis on plasminogen-binding to gp330 and activation by urokinase.
Previous results have shown that the autoantibody eluted from the glomeruli of rats with active Heymann nephritis contain a population of antibodies not only to the putative autoantigen of the disease, gp330, but also to plasminogen. Since gp330 has been shown to serve as a receptor for plasminogen, we have analyzed the effects of autoantibody on plasminogen-binding to gp330 and activation of plasminogen to plasmin by urokinase. Autoantibody does not inhibit the binding of plasminogen to gp330. The binding of autoantibody to plasminogen was shown to be very specific for the compact conformation of glu-plasminogen. The change in the conformation of plasminogen when its lysine-binding sites are occupied or after conversion to plasmin results in a significant decrease in autoantibody-binding. The most significant effect of autoantibody on this system is the inhibition of plasminogen activation to plasmin 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 of rats with active Heymann nephritis does not inhibit the binding of plasminogen to gp330 but does significantly alter the urokinase catalyzed activation of plasminogen to plasmin.
Kanalas
J J
JJ
Department of Pediatrics, University of Texas Health Science Center at San Antonio 78284-7813.
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D001667:Binding, Competitive; D005341:Fibrinolysin; D005921:Glomerulonephritis / Q000276:immunology*; D026541:Heymann Nephritis Antigenic Complex; D007678:Kidney Glomerulus / Q000276:immunology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D010958:Plasminogen / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D001323:Autoantibodies; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator