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.