Nephritogenicity of proteoglycans. III. Mechanism of immune deposit formation

Administration of antibody, directed against glomerular basement membrane (GBM) heparan sulfate-proteoglycan, into a presensitized rat results in the induction of membranous nephropathy with subepithelial immune-complex deposits. In this investigation, we examined the mechanisms responsible for the formation of subepithelial immune-complex deposits in the anti-HS-PG model. In initial experiments, the intravenously administered radioiodinated antibody was seen exclusively localized in the regions of the glomerular capillary wall where the subepithelial deposits were observed. To determine their exclusive localization in the subepithelial space, kinetics of movement of the intravenously administered antibody was investigated. The antibody localized in the inner layers of the GBM within a few minutes after its administration. It equilibrated in the inner and outer layers of the GBM in a matter of a few hours. Then, after 24 hours, it gradually disappeared from the inner layers of the GBM and persisted in the outer layers only. The ready clearance of the antibody from the inner layers may be related to the differential in the kinetics of lateral intrinsic plasma fluid currents within the GBM. The persistence of heterologous antibody exclusively in the outer layers and the availability of host autologous antibodies probably resulted in the development of immune complex deposits in the subepithelial space. The glomeruli devoid of plasma water currents showed no change in the concentration of the antibody in the inner and outer layers of the GBM or mesangial matrix. Also, no antibody binding was observed with the plasmalemma of either the foot processes or visceral epithelia. The data suggest that the biochemical-biophysical properties of the glomerular capillary wall, in concert with its intraglomerular hemodynamics, most likely played a significant role in the development of subepithelial immune-complex deposits in this model.