Anti-GBM Nephritis in the Mouse: Role of Granulocytes in the Heterologous Phase

The role of polymorphonuclear granulocytes (PMNs) was studied in a model of anti-GBM nephritis in mice, in which PMN depletion was induced by total body irradiation of 7.5 Gy. Both in complement-normal B10.D2 new and in C5-deficient B10.D2 old mice, PMN depletion completely prevented the albuminuria occurring after injection of low doses of anti-GBM serum, and severely depressed the albuminuria after injection of high doses. In immunofluorescence, glomerular deposition of antibody and C3 was similar to that in control mice. The glomerular influx of PMNs in both the complement-normal and C5-deficient controls was inhibited to 10% or less of control values. Fibrin deposition or necrosis did not occur. Injection of F(ab')2 fragments of the anti-GBM antibody in non-irradiated mice caused only limited PMN influx and reduced the albuminuria to physiological levels, although the binding of 125I labeled F(ab')2 fragments to the glomeruli was as high as 82% of that of the complete antibody. We conclude that the albuminuria in this model is Fc-dependent and largely, if not completely, dependent on the influx of PMNs in the glomeruli. Among the many experimental models of anti-GBM nephritis, this is the first one in which the heterologous phase is complement-independent but PMN-dependent.