Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. IV. Investigations into the pathogenesis of the model

Abstract

Heterologous immune complex glomerulonephritis can be induced in various strains of rats by one injection of heterologous antibody directed against antigens present in the brush border of the proximal. Although it is generally believed that an immune complex glomerulonephritis is caused by the deposition of soluble immune complexes from the circulation in the glomerular basement membrane, there are reasons for doubting whether this mechanism is also operating in the type of experimental glomerulonephritis presented here. In a study using injections of extra antibody and extra antigen to influence the formation and deposition of immune complexes, it is demonstrated that this type of glomerulonephritis is induced in a state of antibody excess. The theory that only immune complexes formed in antigen excess can deposit in the glomerular basement membrane, warrants the assumption that in our model a different pathogenetic mechanism is operating. The hypothesis is put forward that in the heterologous immune complex glomerulonephritis free antibody crosses the glomerular basement membrane to combine with the antigen. This antigen either crosses the glomerular basement membrane separately or is already present as an integral part of this structure.