Glomerular permeability: In vivo tracer studies with polyanionic and polycationic ferritins

Glomerular permeability: In vivo tracer studies with polyanionic and polycationic ferritins. The influence of molecular charge on glomerular permeability to the globular ferritin molecule in vivo was investigated. Mice (Charles River CD strain) and rats (Munich-Wistar strain) were injected intravenously either with native anionic ferritin or various cationized derivatives with different isoelectric points (pI) and the kidneys were examined by electron microscopy. Native anionic ferritin was almost completely restricted from entry into the glomerular filter at the level of the endothelium and subendothelial layer of the glomerular basement membrane (GBM). Cationized derivatives penetrated the filter in increasing amounts depending on the pI of the tracer. Regardless of charge, all molecules that filtered through the lamina densa of the GBM and reached the subepithelial layer were completely restricted from entry into the urinary space at the level of filtration slits and appeared in phagosomes present in podocytes. Reduction of arterial pressure or cessation of renal blood flow did not influence the movement of ferritin molecules into the GBM. The results are consonant with physiological studies indicating charge dependent restriction of polyanion transport by the mammalian glomerulus. These tracer studies, in conjunction with cytochemical and biochemical evidence for the presence of polyanionic glycoproteins in the glomerular filter, suggest that glomerular restriction of plasma proteins occurs in part by a process similar to that which excludes negatively charged macromolecules in polyanionic gel systems. Permeabilite glomerulaire: Etudes in vivo a l'aide de ferritines polyanioniques et polycationiques comme traceur. L'influence de la charge moleculaire sur la permeabilite glomerulaire a la molecule de ferritine a ete etudiee in vivo . Des souris et des rats Munich-Wistar ont recu, par voie intraveineuse, soit de la ferritine anionique naturelle soit divers derives cationiques ayant divers points isoelectriques (pI). Les reins ont ete examines en microscopie electronique. L'entree de la ferritine naturelle anionique dans le filtre glomerulaire est bloquee au niveau de l'endothelium et de la couche sous-endotheliale de la membrane basale du glomerule (GBM). Les derives cationiques penetrent le filtre en quantite croissante en fonction du pI du traceur. Independamment de la charge, toutes les molecules qui filtrent a travers la lamina densa du GBM et atteignent la couche sous-epitheliale sont bloquees au niveau des fentes de filtration, ne passent pas dans l'espace urinaire et apparaissent dans des phagosomes presents dans les podocytes. La diminution de la pression arterielle ou l'interruption du debit sanguin renal n'influencent pas le mouvement des molecules de ferritine dans le GBM. Ces resultats sont en accord avec les travaux physiologiques qui indiquent une restriction du transport des polyanions, par le glomerule de mammifere, dependante de la charge. Ces etudes de traceurs ainsi que les preuves cytochimiques et biochimiques de la presence de glycoproteines polyanioniques dans le filtre glomerulaire, suggerent que la restriction du passage glomerulaire des proteines plasmatiques est en partie realisee par un processus similaire a celui qui exclue les macromolecules chargees negativement dans les systemes de gels polyanioniques.