Rapid and focal loss of negative charge associated with mononuclear cell infiltration early in nephrotoxic serum nephritis

We have examined the morphologic changes and alterations in negative charge, as demonstrable with colloidal iron at pH 2, in rat glomeruli, 15 min, 0.5, 1, and 2 hours after injecting rabbit antirat kidney serum (NTS). As early as 15 min following NTS administration, mononuclear (MN) cells, resembling lymphocytes, were evident in glomerular capillary lumens. By 0.5 hour, along with this MN cell infiltrate and prior to overt proteinuria, there was focal loss of negative charge from the endothelial cell coat and lamina rara interna (LRI). At 2 hours, polymorphonuclear leukocytes (PMN) had replaced the MN cells as the infiltrating cell type in the glomerular capillaries, and focal loss of negative charge had extended to include portions of the lamina rara externa (LRE) and epithelial cell coat. When animals were either irradiated or given rabbit antirat lymphocyte serum (ALS) 24 hours prior to NTS administration, the 24-hour proteinuria was significantly less than it was in controls (irradiated, 19 ± 6 mg/24 hr; control, 130 ± 13 mg/24 hr; ALS, 29 ± 5 mg/24 hr; control, 125 ± 7 mg/24 hr). These treatments were associated with markedly fewer cells per glomeruli than there were in controls at early time periods (15 min and 0.5 hour) and no loss of negative charge from the glomerular wall. This study demonstrated that MN cell infiltration occurred rapidly after NTS, and this infiltration correlated with focal loss of negative charge from the glomerular filtration barrier, and with proteinuria.