Effect of increased glomerular permeability on the localization of immune aggregates and protamine-heparin aggregates in the rat.
The effect of adriamycin (doxorubicin)-induced proteinuria, which is characterized by a defect in the glomerular size selective filter with intact charge barrier function, was studied on the glomerular localization of immune aggregates and protamine-heparin aggregates. For that purpose, passive Heymann's nephritis and protamine-heparin aggregates were induced in rats with adriamycin nephrosis (mean proteinuria 311 mg/24 hours at 4 weeks after intravenous administration of adriamycin, 6.5 mg/kg). The distribution of immune aggregates and protamine-heparin aggregates in the proteinuric rats was studied by immunofluorescence and electron microscopy and compared with glomerular aggregate localization in untreated control rats. The amount of glomerular aggregates was measured by semiquantative immunofluorescence. The results showed that glomerular localization of immune aggregates in nephrotic rats was similar to that in control rats. The aggregates were present in a granular distribution along the epithelial side of the glomerular basement membrane and also in areas of widespread foot process obliteration, in a slightly lesser amount than in controls. The localization of protamine-heparin aggregates in the glomerular capillary wall of nephrotic rats was identical with that in controls. No mesangial accumulation of immune or protamine-heparin aggregates was found. The results indicate that increased permeability per se has no effect on the glomerular distribution of macromolecular aggregates. In addition, this study shows that in adriamycin-induced nephrosis--in contrast to what has been reported in aminonucleoside nephrosis--(a) the glomerular capillary wall has maintained the antigens that take part in in situ immune complex formation in passive Heymann's nephritis, (b) the intact glomerular charge barrier is capable of binding protamine-heparin aggregates, and (c) no mesangial accumulation of aggregates occurs, suggesting a normal mesangial function in this model.
D000818:Animals; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000032:analysis*; D001485:Basement Membrane / Q000276:immunology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate; D006493:Heparin / Q000032:analysis*; D007672:Kidney Cortex / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000276:immunology; D008871:Microvilli / Q000276:immunology; D009401:Nephrosis / Q000139:chemically induced / Q000276:immunology; D011479:Protamines / Q000032:analysis*; D011507:Proteinuria / Q000139:chemically induced; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D051381:Rats
D000936:Antigen-Antibody Complex; D011479:Protamines; D011692:Puromycin Aminonucleoside; D004317:Doxorubicin; D006493:Heparin