Size and charge selective permeability defects induced in glomerular basement membrane by a polycation

Abstract

Polyethyleneimine (PEI) was given intravenously to rats followed by native ferritin or one of three cationic ferritins. After 15 min kidneys were fixed for electron microscopy. Controls (C) received vehicle without PEI, followed by the appropriate ferritin. PEI-induced permeability change was measured as the ratio (PEI/C) of counted ferritin particles within the glomerular basement membrane (GBM) in the corresponding PEI and control groups. The ratio PEI/C for each tracer was: NF (pI = 4.5-4.8)-107; CF (pI = 7.5-8.2)-3.3; CF (pI = 8.0-8.7)-1.7; and CF (pI = 8.7-9.0)-0.9. When ferritin localization in the subendothelial layer of the GBM was examined separately, PEI/C was increased for all ferritins including the most cationic species. After PEI, GFR and RBF decreased proportionately by half; thus, filtration fraction remained constant. Reduction of renal perfusion pressure to 40 mm Hg showed no alteration of ferritin permeation into the GBM. Thus, PEI effects on ferritin localization in the GBM could not be ascribed to renal hemodynamic perturbations. If the effect of PEI on GBM permeability were to be mediated exclusively by neutralization of the charge barrier, the index PEI/C should be increased for NF, but decreased for all CF. The results show a marked effect of PEI on the charge barrier (PEI/C > 100 for NF). But, PEI also enhanced total GBM permeation by CF (7.5-8.2) and CF (8.0-8.7), and increased subendothelial GMB permeation for CF (8.7-9.0). An inverse relationship of the effect of PEI to the cationic charge on CF was evident. These paradoxical results can be explained if polycations (including CF) not only neutralize anionic sites, but distort GBM gel structure, thereby altering porosity.