Glomerular permeability: focal loss of anionic sites in glomeruli of proteinuric mice with lupus nephritis.

The charge-based barrier of the glomerular capillary filter was investigated in normal mice and in mice with immune complex lupus nephritis. Cationized ferritin (CF), pI 7.7 To 8.5, was used as a molecular probe of fixed anionic sites. Mice with various degrees of proteinuria and severity of glomerulonephritis were systemically injected with CF and their glomeruli studied ultrastructurally employing morphometric methods. A decreased and erratic localization of CF was observed in the lamina rara externa, in the intervening basement membrane between immune deposits, and in basement membrane projections, areas previously shown to be abnormally permeably to a large anionic protein. In small numbers, CF molecules were found in residual epithelial slits and in the urinary space. In normal mice, CF regularly labeled the laminae rarae of the glomerular basement membrane and the slit pore area but not leak into the urinary space. Such differences in CF localization in capillary loops of proteinuric and normal mice were confirmed by morphometric estimate of particle counts. Focal areas of increased permeability to anionic protein are deficient of and/or exhibit a disorderly redistribution of fixed anionic sites.