Experimental nephrosis: interassociation of proteinuria with impaired lymphocyte blastogenesis

The drug puromycin aminonucleoside (PA), used to induce an experimental nephrosis in rats, inhibited the blastogenic response of normal rat spleen cells when cultured in vitro with autologous or heterologous serum. Only at final PA concentrations of less than 5 microgram/ml did PHA induce normal blastogenesis. When PA was unilaterally perfused through the rat kidney a nephrosis developed, characterized by massive proteinuria. Microscopically, the foot process fusion and mesangial cell increase were similar to that seen in human steroid-responsive nephrotic syndrome. Once proteinuria had developed, there was marked suppression of the lymphocyte blastogenic response of the nephrotic rat spleen cells when cultured in autologous sera. Neither proteinuria nor inhibited blastogenesis was found in animals perfused with a buffered salt solution. Animals which were perfused with PA, nephrectomized 2 days after perfusion, and did not show proteinuria, had suppressed lymphocyte blastogenesis after stimulation with PHA. However, the degree of stimulation by the spleen cells of these animals was similar to that from control perfused and nephrectomized animals. Therefore, the aberration in lymphocyte response was consistent with the development of the nephrosis and proteinuria.