Rapid and severe proteinuria induced in rats by antibody against cultured rat glomerular epithelial cells.

The aim of this study was to investigate the role of glomerular visceral epithelial cell (GEC) antigens in the induction of proteinuria. An antibody (anti-GECIg) was produced by rabbit immunization with membrane extracts prepared from a clonal GEC line, SGE1, from the isolated rat renal glomeruli. A one-shot intraperitoneal injection of anti-GECIg (day 0) induced rapid and severe proteinuria in rats, reaching a peak on day 2 (mean value, 425 mg/24h), then gradually decreased to normal levels by day 10. By direct immunofluorescence, fine granular binding of anti-GECIg along the glomerular capillary walls was observed within 24 h. Electron microscopy and immunoelectron microscopy revealed GEC alterations consisting of extensive retraction of the foot processes, vacuolar changes in the cytoplasm, microvillous transformation of the cell surface, and binding of anti-GECIg to the surface of the foot process, mainly to its soles. Two major components with Mr of 108,000 and 39,000 were identified by immunoblotting assay using SGE1 cell membrane extracts and anti-GECIg. This model of rat nephropathy induced by anti-GECIg hopefully will lead to a greater understanding of the mechanism by which proteinuria is induced and developed.