Immunoenzymatic study of the protein pathway through the glomerular barrier in rat glomerulonephritides

Circulating anti-horseradish peroxidase (HRP) IgG antibodies were used in the rat to study the glomerular leakage of proteins in glomerulonephritis (GN) induced by aminonucleoside (AN) and in glomerulonephritis induced by mercuric chloride to produce anti-glomerular basement membrane (GBM) antibodies. In ANGN, autologous albumin and fibrinogen were also detected by immunoperoxidase techniques. In both types of GN, the proteins studied were observed in the glomerular urinary space and proximal tubular cells. No channels were visible in the lamina densa. No accumulation of proteins was seen under the epithelial slits that were not closed. In ANGN, accumulation of proteins was observed in the subepithelial space where the podocytes act as a barrier (closed slits, subepithelial blind pockets, areas covered by broad sheets of cytoplasm), but no accumulation was seen in the lamina rara externa under normal or enlarged slits and areas of large epithelial cytoplasm detachment. Statistical analysis showed that in ANGN, at the time of maximal proteinuria, the number of "micropinocytotic" vesicles in the GBM-embedded part of podocytes was not increased as compared with controls. Such vesicles were not labeled. We conclude that in both types of GN, the permeability of the GBM is diffusely increased and that the plasma proteins pass into the urinary space via an extracellular pathway.