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Determinants of glomerular localization of subepithelial immune deposits effects of altered antigen to antibody ratio steroids vasoactive amine antagonists and amino nucleoside of puromycin on passive heymann nephritis in rats



Determinants of glomerular localization of subepithelial immune deposits effects of altered antigen to antibody ratio steroids vasoactive amine antagonists and amino nucleoside of puromycin on passive heymann nephritis in rats



Laboratory Investigation 41(1): 89-99



The role of circulating immune complex deposition versus in situ complex formation in membranous nephropathy is controversial. Passive Heyman nephritis in rats resembles membranous nephropathy in man and was induced by injection of sheep antibody to rat proximal tubular epithelial cell brush border antigen (anti-Fx1A). Minutes after injection of 1 ml of anti-Fx1A, subepithelial immune deposits were seen by immunofluorescence and EM, and proteinuria appeared within 5 days. The effects of alterations in the dose of administered antibody, corticosteroid therapy and vasoactive amine blockade on the development of subepithelial deposits and consequent proteinuria were studied. Variation of the dose of anti-Fx1A from 0.25 ml to 1 ml resulted in a progressive increase in the size and number of glomerular capillary wall deposits, but no alterations in their distribution. Only those rats which received 1 ml became proteinuric within 5 days. Corticosteroid therapy and vasoactive amine blockade, begun 24 h prior to the induction of passive Heymann nephritis and continued until termination of the study 5 days later, had no effect on the amount or site of immune complex formation, nor on the extent of proteinuria as compared to untreated controls. In rats with unilateral proteinuria produced by the selective perfusion of 1 kidney with aminonucleoside of puromycin 7 days prior to the induction of passive Heymann nephritis, there was a marked reduction of subepithelial deposits in the perfused kidney as compared to the nonperfused contralateral kidney. In this model of membranous nephropathy, systemic factors play little role in the development of subepithelial deposits, whereas local factors are critical. These findings are consistent with the hypothesis that subepithelial immune deposits form locally.

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Accession: 005120083

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PMID: 376941


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