Tubular antigen-associated renal disease in New Zealand white rabbits. II. Investigation of mediators of glomerular injury: localization and characterization of the glomerular capillary wall antigen

Abstract

Mediation of the glomerular lesion and proteinuria produced by sheep antirabbit F x 1A globulin (SAFG) in rabbits was examined by prior treatment with cobra venom factor and nitrogen mustard. SAFG binding and proteinuria at 24 h were independent of complement or leucocytes but dose dependent. SAFG reacted by immunoblot with a wide range of antigens in deoxycholate extracts of rabbit glomeruli and autologous F x 1A including eight prominent shared bands of 29-128 kd. Immunogold electron microscopy has revealed the in vivo glomerular binding of SAFG as discrete, nonlinear and predominantly within the laminae rarae, in association with epithelial and particularly endothelial components of the glomerular capillary wall. In vitro binding was prominent on the endothelium. Proteinuria in this model is mediated by antibody without requirement for complement or leucocytes. The putative antigen(s) is/are associated with components of the glomerular capillary wall which share epitopes with autologous tubular F x 1A. This model is an example of an in situ immune complex glomerular nephritis and is distinct from the classical anti-F x 1A model, passive Heymann's nephritis in the rat.