PATHOBIOLOGY OF CULTURED GLOMERULAR EPITHELIAL CELLS

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The aim of this project is to study the response of cultured glomerular visceral epithelial cells to nonimmunologic and immunologic injury. Glomerular epithelial cells appear to play a role in puromycin aminonucleoside nephrosis and Heymann nephritis in rat. These experimental models closely resemble human glomerular diseases - minimal change nephrotic syndrome and membranous nephropathy, respectively. We have previously shown that these receptors bear receptors for C3, antigens of Heymann nephritis on their surface and that they synthesize heparan sulfate proteoglycan. Sialic acid residues, richly deposited on these epithelial cells, and, glomerular heparan sulfate are said to be involved in glomerular barrier function against protein loss. Complement system including the membrane attack complex is known to be prominently involved in pathogenesis of many glomerular diseases including Heymann nephritis. Employing the above properties, specifically, we propose to study the following: I. Effect of puromycin aminonucleoside (nonimmunologic injury) on Heymann nephritis related antigen, heparan sulfate and sialic acid contents of glomerular epithelial cells. II. A. Effect of binding of antibody to Heymann nephritis related antigen located on glomerular epithelial cells (immunologic injury) on expression of C3 receptors, content of heparan sulfate and sialic acid. B. Effects of binding of C3 ligands, membrane attack complex, alone or in combination (immunologic injury) on content of heparan sulfate and sialic acid. Methods employed will consist of cell culture of glomerular epithelial cells, quantitative immunoperoxidase, standard rosette techniques using sheep erythrocytes as indicator particles. In immunoperoxidase reactions, highly purified, well described specific antibodies will be used. Standard parametric and nonparametric statistical methods will be used in analysis of results. Our results will advance understanding the role of glomerular visceral epithelial cells in the two experimental renal disease models which are prototypes of common human glomerulopathies.