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Complement system promotes transfer of immune complex across glomerular filtration barrier
Y Fujigaki1, S R Batsford, D Bitter-Suermann
1Institut für Medizinische Mikrobiologie und Hygiene, Abteilung Immunologie, Germany.
Background:
The solubilizing effect of complement (C) on immune complexes (IC) in the fluid phase is well known, however effects on tissue-deposited IC have not been analyzed in detail. We studied the influence of C depletion on the movement of IC across the glomerular basement membrane in a rat model of passive in situ IC nephritis.
Experimental Design:
The left kidneys of intact rats, rats given cobra venom factor (C-depleted) or rats given anti-polymorphonuclear granulocyte antiserum (PMN-depleted) were perfused with cationized ferritin (electron-dense tracer antigen), followed by intravenous injection of rabbit anti-ferritin antibody 15 minutes later. The glomerular distribution of rabbit IgG (antibody) and rat C3 was visualized by immunogold staining.
Results:
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 virtually all 3 IC components were localized on the subepithelial side of the 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 hours, two patterns of IC distribution within individual glomeruli could be distinguished. About 2/3 of the capillary wall area revealed a distribution similar to the C-intact animals; however in 1/3 of the capillary 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 serum C3 level had returned to 60% of normal. On the other hand, the distribution of IC in polymorphonuclear leukocyte-depleted, C-intact rats, showed no difference to that in control nephritic rats. Proteinuria was significantly decreased in both C-depleted rats and polymorphonuclear leukocyte-depleted rats. Thus, enhanced glomerular permeability itself does not guarantee complete, rapid IC movement.
Conclusions:
The C system promotes effective transfer of IC across the glomerular basement membrane, probably due to the solubilizing effect of C on IC lattices.