THE POSSIBLE ROLES OF HYPERLIPIDEMIA AND MONONUCLEAR-CELLS IN GLOMERULI IN PUROMYCIN AMINONUCLEOSIDE NEPHROSIS IN RATS

The possibility that hyperlipidemia and an increase of mononuclear cel ls in the glomeruli could participate in the pathogenesis of minimal c hange glomerulopathy was evaluated in puromycin aminonucleoside (PAN) nephrosis in rats. Significant increases in intraglomerular CD4-, IL-2 -receptor (R)- and ED-1-positive cells were found in PAN rats. Urinary protein excretion and mononuclear cells in the glomeruli of 1% choles terol diet-fed rats significantly increased, compared with standard di et feeding. Moreover, administration of a subnephrogenic dose of PAN i n cholesterol diet-fed rats substantially increased urinary protein ex cretion and mononuclear cells in the glomeruli. Additionally, antihype rlipidemia agents and immunosuppressive agents prevented urinary prote in excretion and increases of CD4-, IL-2R- and ED-1-positive cells in the glomeruli of PAN nephrotic rats. Monoclonal antibodies directed ag ainst these cells also prevented urinary protein excretion. These resu lts suggest that CD4-, IL-2R- and ED-1-positive cells and hyperlipidem ia are involved in the progression, but not the pathogenesis, of PAN.