Glomerular epithelial alterations resulting from sialic acid surface coat removal

Abstract

Glomerular epithelial alterations resulting from sialic acid surface coat removal. An in vitro model system for studying kidney glomeruli was used to investigate the effects of glomerular epithelial sialic acid surface coat removal on the fine structure of these cells. The glomeruli exposed on the surfaces of rat kidney slices were incubated in either oxygenated normothermic Tyrode's balanced salt solution or culture medium, each with and without the enzyme neuraminidase. After 6 hours of incubation in Tyrode's or culture medium alone, the only significant alteration of the glomerular epithelium was an increase in number and length of free surface microvilli and an increase in cytoplasmic lipid inclusions. After 3 hours of incubation in these solutions plus neuraminidase (0.067 U/ml of solution), there was a significant reduction in the glomerular sialic acid surface coat as determined by the colloidal iron staining technique. Coincident with this sialic acid removal, there was a loss of podocyte foot processes and filtration slits and the formation of numerous knoblike projections of the plasmalemma over the glomerular epithelium. By transmission electron microscopy, it appeared that junctional complexes had formed between many podocyte processes and that these processes had retracted toward the cell body. Also noted was the displacement of filtration slit diaphragms away from the glomerular basal lamina and an apparent extensive folding of these diaphragms. Samples examined after 6 hours of incubation in neuraminidase appeared similar to the 3 hour samples except that most of the knobby projections of the glomerular epithelial plasmalemma were gone. The foregoing fine structural alterations resulting from glomerular epithelial sialic acid surface coat removal closely parallel changes exibited by these cells during puromycin aminonucleoside nephrosis. The possible significance of these fine structural changes in the etiology of glomerular disease is discussed. Modifications epitheliales glomerulaires consecutives a l'ablation de la couche superficielle d'acide sialique. Un modele in vitro d'etude des glomerules renaux a ete employe pour etudier les effets de l'ablation de la couche superficielle d'acide sialique sur la structure microscopique de ces cellules. Les glomerules exposes a la surface de tranches de reins de rats onte ete incubes soit dans du Tyrode oxygene et rechauffe, soit dans du milieu de culture avec ou sans neuramidase. Apres 6 heures d'incubation dans le Tyrode ou le milieu de culture seuls, les seules modifications significatives de l'epithelium glomerulaire sont une augmentation du nombre et de la longueur des microvillosites libres a la surface et une augmentation des inclusions lipidiques du cytoplasme. Apres 3 heures d'incubation dans ces solutions additionnees de neuramidase (0,067 U/ml de solution) il y a une diminution significative de la couche superficielle d'acide sialique objectivee par la coloration au moyen du fer colloidal. En meme temps on observe une diminution des processus pedicules des podocytes et des fentes de filtration et la formation de nombreuses projections bosselees du plasmalemme sur l'epithelium glomerulaire. En microscopie electronique par transmission il apparait que des complexes jonctionnels se sont formes entre de nombreux processus pedicules et que ces processus se sont retractes contre le corps cellulaire. On remarque aussi un deplacement des diaphragmes des fentes de filtration a distance de la couche basale du glomerule et une plicature apparente de ces diaphragmes. Les echantillons etudies apres 6 heures d'incubation dans la neuramidase paraissent semblables a ceux etudies apres 3 heures, a ceci pres que la plupart des projections bosselees du plasmalemme de l'epithelium glomerulaire ont disparu. Les modifications ainsi decrites consecutives a l'ablation de la couche superficielle d'acide sialique sont tres semblables a celles observees au cours de la nephrose induite par la puromycine. La signification possible de ces modifications structurales dans l'etiologie de l'atteinte glomerulaire est discutee.