Altered glomerular permeability as a result of focal detachment of the visceral epithelium.
Changes in the permeability of the glomerular capillary wall (GCW) to native ferritin (NF), following detachment of the visceral epithelium from the glomerular basement membrane (GBM) were investigated. Detachment was induced by either perfusing kidneys with highly purified neuraminidase or by the induction of nephrosis through administration of puromycin aminonucleoside (PAN). Both experimental treatments resulted in marked glomerular ultrastructural changes which were characterized by focal detachment of the visceral epithelium from the GBM, replacement of the normal pattern of interdigitating foot processes with flattened expanses of continuous epithelium at certain areas of the GCW, and a generalized loss of sialic acid-rich epithelial cell cost in areas where the epithelium was detached as well as where it remained adherent. These changes were more frequent and prominent in the paramesangial regions of the glomeruli. When experimentally treated kidneys were perfused with NF, the tracer leaked into the urinary spaces in those areas of the GBM where the epithelium was detached. By contrast, in those areas of the GCW where the epithelium remained adherent, the tracer localized within the GBM mainly at the level of the lamina rara interna (LRI), and none of it appeared in the urinary spaces. Nephrotic and neuraminidase control kidneys were ultrastructurally normal, NF localizing mainly in the inner layers of the GBM. These data are consistent with the idea that the firm attachment of the epithelial foot processes to the GBM plays a vital role in determining the permselectivity properties of the GCW to plasma macromolecules.
D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D002199:Capillary Permeability; D004848:Epithelium / Q000473:pathology; D005293:Ferritins / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009401:Nephrosis / Q000473:pathology; D009439:Neuraminidase / Q000494:pharmacology; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011692:Puromycin Aminonucleoside; D005293:Ferritins; D009439:Neuraminidase