Cationic macromolecule-induced nephrotic syndrome in rabbits. Lack of immune complex involvement.
Rabbits given a single intravenous injection of highly cationised horse spleen ferritin (isoelectric point greater than 9.5), 2 to 100 mg/kg of body weight, frequently developed glomerulonephritis, and a substantial proportion became nephrotic. The disease usually remitted spontaneously. Renal tissue obtained before onset of proteinuria (by biopsy), during the acute phase and in the phase of remission, was examined for the presence of cationized ferritin, rabbit IgG, and C3 by immunofluorescence. Electron microscopy was performed on material prepared conventionally and after treatment with polyethyleneimine (to visualize fixed anionic sites in the glomeruli). Cationic ferritin molecules initially bound to the fixed anionic sites in the glomerular basement membrane but disappeared before the onset of proteinuria (6 +/- 3 days). Glomerular deposition of rabbit immunoglobulin or complement was not seen, and electron microscopy did not reveal deposits in the glomerular capillary walls. This makes it unlikely that immune complexes play a role in the pathogenesis of the induced disease. The striking features were extensive loss of epithelial foot processes and pronounced loss of negative charge from the glomerular basement membrane and from the epithelial cell surface coat. These changes preceded onset of proteinuria and, by reference to those animals not developing proteinuria, were seen to be closely linked to the subsequent development of proteinuria. It appears that the transient interaction of a cationic, macromolecular protein antigen with the fixed anionic sites in the glomerular basement membrane can set a chain of events in motion that leads to loss of negative charge and epithelial cell withdrawal, ultimately resulting in proteinuria.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001485:Basement Membrane / Q000473:pathology; D002412:Cations; D004848:Epithelium / Q000648:ultrastructure; D005293:Ferritins / Q000378:metabolism; D006651:Histocytochemistry; D007678:Kidney Glomerulus / Q000378:metabolism; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D009404:Nephrotic Syndrome / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011094:Polyethyleneimine; D011507:Proteinuria / Q000652:urine; D011817:Rabbits
D000936:Antigen-Antibody Complex; D002412:Cations; D046911:Macromolecular Substances; D011094:Polyethyleneimine; D005293:Ferritins