Complement and monocytes are essential for provoking glomerular injury in passive Heymann nephritis in rats. Terminal complement components are not the sole mediators of proteinuria.

Complement but not polymorphonuclear granulocytes (PMN) causes glomerular injury in passive Heymann nephritis in rats. We have now identified monocytes as another important mediator in this model. Passive Heymann nephritis was induced in Wistar rats by intravenous injection of sheep anti-rat Fx1A antiserum. Four groups (all receiving anti-rat Fx1A antiserum) were studied: (a) rats given normal sheep globulin (nephritic controls), (b) rats given sheep anti-rat PMN globulin (PMN-depleted), (c) rats given sheep anti-rat monocyte globulin (monocyte-depleted), (d) rats injected with cobra venom factor (complement-depleted). In vitro specificity controls for anti-cell antisera were made by cytotoxicity tests and inhibition of phagocytosis. In vivo specificity controls were performed in heterologous Masugi nephritis (PMN-dependent) and accelerated Masugi nephritis (monocyte-dependent). Complement and monocyte depletion significantly delayed the onset of proteinuria (p less than 0.001 versus nephritic controls on day 5), PMN depletion had no significant effect. Monocyte infiltration was seen in control nephritic rats, but monocyte depletion prevented this influx. In the monocyte-depleted group, no differences in glomerular deposition of C3, C9, and C5b-9 were seen in comparison to the nephritic control rats. Serum C3 levels were comparable in groups a, b, and c, the complement system was biologically active in the monocyte depleted-group (c), and the amount of anti-Fx1A antibody bound was the same in all groups. This shows that, besides complement, monocytes are required for induction of renal damage in passive Heymann nephritis. The concept of a sole role for complement in glomerular immune injury involving subepithelial immune deposits should be reconsidered.