COMPLEMENT-SYSTEM PROMOTES TRANSFER OF IMMUNE-COMPLEX ACROSS GLOMERULAR-FILTRATION BARRIER

BACKGROUND: The solubilizing effect of complement (C) on immune comple xes (IC) in the fluid phase is well known, however effects on tissue-d eposited IC have not been analyzed in detail. We studied the influence of C depletion on the movement of IC across the glomerular basement m embrane in a rat model of passive in situ IC nephritis. EXPERIMENTAL D ESIGN: The left kidneys of intact rats, rats given cobra venom factor (C-depleted) or rats given anti-polymorphonuclear granulocyte antiseru m (PMN-depleted) were perfused with cationized ferritin (electron-dens e tracer antigen), followed by intravenous injection of rabbit anti-fe rritin antibody 15 minutes later. The glomerular distribution of rabbi t IgG (antibody) and rat C3 was visualized by immunogold staining. RES ULTS: In intact, nephritic rats (non C-depleted), the distribution of antigen, antibody, and C3 (IC) was mainly subendothelial 2 and 6 hours after antibody injection, at 24 hours about 75% and by 48 hours virtu ally all 3 IC components were localized on the subepithelial side of t he glomerular basement membrane in all glomeruli. In C-depleted rats, the distribution of IC was as in intact rats, up to 6 hours. At 24 hou rs, two patterns of IC distribution within individual glomeruli could be distinguished. About 2/3 of the capillary wall area revealed a dist ribution similar to the C-intact animals; however in 1/3 of the capill ary wall area, IC was still predominantly subendothelial at 24 hours. By 48 hours, some accumulation in the lamina densa was noted. At day 7 , some IC was still subendothelial, in limited areas, even though seru m C3 level had returned to 60% of normal. On the other hand, the distr ibution of IC in polymorphonuclear leukocyte-depleted, C-intact rats, showed no difference to that in control nephritic rats. Proteinuria wa s significantly decreased in both C-depleted rats and polymorphonuclea r leukocyte-depleted. rats. Thus, enhanced glomerular permeability its elf does not guarantee complete, rapid IC movement. CONCLUSIONS: The C system promotes effective transfer of IC across the glomerular baseme nt membrane, probably due to the solubilizing effect of C on IC lattic es.