Skip to main content

Alterations in the sialic acid content of the rat glomerular filter in aminonucleoside nephrosis

Virchows Archiv B volume 50, Article number: 237 (1986) Cite this article

Summary

A daily injection protocol with puromycin aminonucleoside (PAN) causes loss of sialic acid from the glomerular filter. These changes have been studied previously by colloidal iron staining, but we have recently shown that phosphotungstic acid (PTA) at low pH allows the demonstration of sialic acid groups in the glomerular basement membrane in ultrathin sections of glycolmethacrylate(GMA)-embedded rat kidney. With this technique the slit diaphragm is seen as a continuation of the luminal cell coat and the method also gives an idea of the sialic acid distribution at the podocyte plasma membrane. The availability of this method made it possible to reevaluate the results obtained earlier in aminonucleoside (PAN) nephrosis indicating a decrease in the sialic acid content of the glomerulus.

Although there are changes in the epithelial architecture, the ultrastructural appearances of the basement membrane are only slightly altered in PAN nephrosis. Detachment of epithelial cells was variable in different animals. Seven days after the first injection of PAN, staining with PTA revealed local defects in the lamina rara externa which later became more extensive. In PAN-treated animals the luminal cell coat showed reduced staining and large areas of the plasma membrane were completely devoid of a cell coat. These changes coincided with the onset of heavy proteinuria.

The results indicate that both the basement membrane and the epithelial plasma membrane are affected in PAN nephrosis, as revealed by decreased staining for sialic acid-containing molecules in the basement membrane and by changes in the epithelial cell coat. The defects in the cell coat material point to functional alterations at the level of the slit pores and it is suggested that the decrease in sialic acid content of the lamina rara externa may be partly responsible for defects in the size-selective filtration barrier in PAN nephrosis.

This is a preview of subscription content, access via your institution.

References

  • Abrahamson DR, Hein A, Caulfield JP (1983) Laminin in glomerular basement membrane of aminonucleoside nephrotic rats. Increased proteinuria induced by antilaminin immunoglobulin. Lab Invest 49:38–47

    PubMed  CAS  Google Scholar 

  • Alcorn D, Ryan GB (1981) Distribution of anionic groups in the glomerular capillary wall in rat nephrotoxic nephritis and aminonucleoside nephrosis. Pathology 13:37–50

    PubMed  Article  CAS  Google Scholar 

  • Andrews PM (1977) A scanning and transmission electron microscopic comparison of puromycin aminonucleoside-induced nephrosis to hyperalbuminuria-induced proteinuria with emphasis on kidney podocyte pedicel loss. Lab Invest 36:183–197

    PubMed  CAS  Google Scholar 

  • Andrews PM (1981) Cationized ferritin binding to anionic surfaces in normal and aminonucleoside nephrotic kidneys. Am J Anat 162:89–106

    PubMed  Article  CAS  Google Scholar 

  • Barnes JL, Radnik RA, Gilchrist EP, Venkatachalam MA (1984) Size and charge selective permeability defects induced in glomerular basement membrane by a polycation. Kidney Int 25:11–19

    PubMed  Article  CAS  Google Scholar 

  • Bertolatus JA, Foster SJ, Hunsicher LG (1984) Stainable glomerular basement membrane polyanions and renal hemodynamics during hexadimethrine-induced proteinuria. J Lab Clin Med 103:632–642

    PubMed  CAS  Google Scholar 

  • Blau EB, Michael AF (1972) Rat glomerular glycoprotein composition and metabolism in aminonucleoside nephrosis. Proc Soc Exp Biol Med 141:164–172

    PubMed  CAS  Google Scholar 

  • Caulfield JP (1979) Alteration in the distribution of Alcian Blue staining fibrillar anionic sites in the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest 40:503–511

    PubMed  CAS  Google Scholar 

  • Caulfield JP, Farquhar MG (1978) Loss of anionic sites from the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest 39:505–512

    PubMed  CAS  Google Scholar 

  • Caulfield JP, Reid JJ, Farquhar MG (1976) Alterations of the glomerular epithelium in acute aminonucleoside nephrosis. Evidence for formation of occluding junctions and epithelial cell detachment. Lab Invest 34:43–59

    CAS  Google Scholar 

  • Courtoy PJ, Timpl R, Farquhar MG (1982) Comparative distribution of laminin, type IV collagen and fibronectin in the rat glomerulus. J Histochem Cytochem 30:874–886

    PubMed  CAS  Google Scholar 

  • Geyer G (1977) Elektronenmikroskopische Histochemie. Teil 1. Nachweis und Kontrastierungsmethoden für Kohlenhydrate, Proteine und Aminosäuren, Nucleinsäuren, Lipiden und Mineralstoffen. In: Graumann W, Neumann K (eds) Handbuch der Histochemie. Gustav Fisher Verlag, Stuttgart, New York, pp 12–17

    Google Scholar 

  • Hunsicher LG, Shearer TP, Schaffer SJ (1981) Acute reversible proteinuria induced by infusion of the polycation hexadimethrine. Kidney Int 20:7–17

    Article  Google Scholar 

  • Kanwar YS (1984) Biology of disease. Biophysiology of glomerular filtration and proteinuria. Lab Invest 51:7–21

    PubMed  CAS  Google Scholar 

  • Kanwar YS, Farquhar MG (1980) Detachment of endothelium and epithelium from the glomerular basement membrane produced by kidney perfusion with neuraminidase. Lab Invest 42:375–384

    PubMed  CAS  Google Scholar 

  • Kanwar YS, Jacubowski M (1984) Unaltered anionic sites of glomerular basement membrane in aminonucleoside nephrosis. Kidney Int 25:613–618

    PubMed  Article  CAS  Google Scholar 

  • Kanwar YS, Rosenzweig LJ (1982) Altered glomerular permeability as a result of focal detachment of the visceral epithelium. Kidney Int 21:565–574

    PubMed  Article  CAS  Google Scholar 

  • Kerjaschki D, Vernillo AT, Farquhar MG (1985) Reduced sialylation of podocalyxin — the major sialoprotein of the rat kidney glomerulus — in aminonucleoside nephrosis. Am J Pathol 118:343–349

    PubMed  CAS  Google Scholar 

  • Leduc EH, Bernhard W (1967) Recent modification of the glycolmethacrylate embedding procedure. J Ultrastruct Res 19:196–199

    PubMed  Article  CAS  Google Scholar 

  • Michael AF, Blau E, Vernier RL (1970) Glomerular polyanion. Alteration in aminonucleoside nephrosis. Lab Invest 23:649–657

    PubMed  CAS  Google Scholar 

  • Mynderse LA, Hassell JR, Kleinman HK, Martin GR, Marinez-Hernandez A (1983) Loss of heparan sulfate proteoglycan from glomerular basement membrane of nephrotic rats. Lab Invest 48:292–302

    PubMed  CAS  Google Scholar 

  • Nevins TE, Gaston T, Basgen JM (1984) Quantitative indexes of aminonucleoside induced nephrotic syndrome. Am J Pathol 117:30–36

    PubMed  CAS  Google Scholar 

  • Olson JL, Rennke HG, Venkatachalam MA (1981) Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats. Lab Invest 44:271–279

    PubMed  CAS  Google Scholar 

  • Orci L, Kunz A, Amherdt M, Brown D (1984) Pertubation of podocyte plasma membrane domains in experimental nephrosis. A lectin binding and freeze-fracture study. Am J Pathol 117:286–297

    PubMed  CAS  Google Scholar 

  • Quatacker J (1983) Detection of neuraminidase-sensitive molecules in the laminae rarae of the rat glomerular basement membrane. Biol Cell 48:21a

    Google Scholar 

  • Quatacker JR (1985) Demonstration of sialic acid groups in the glomerular basement membrane of the rat with phosphotungstic acid at low pH. Histochem J 17:201–212

    PubMed  Article  CAS  Google Scholar 

  • Reale E, Luciano L, Kuhn KW (1983) Ultrastructural architecture of proteoglycans in the glomerular basement membrane. A cytochemical approach. J Histochem Cytochem 31:662–668

    PubMed  CAS  Google Scholar 

  • Ryan GR, Rodewald R, Karnovsky MJ (1975) An ultrastructural study of the glomerular diaphragm in aminonucleoside nephrosis. Lab Invest 33:461–468

    PubMed  CAS  Google Scholar 

  • Scott JE, Glick D (1971) The invalidity of “phosphotungstic acid as a specific electron stain for complex carbohydrates”. J Histochem Cytochem 19:63–64

    PubMed  CAS  Google Scholar 

  • Timpl R, Rohde H, Risteli L, Ott U, Roley PG, Martin GR (1982) Laminin. Meth Enzymol 82:831–837

    PubMed  CAS  Article  Google Scholar 

Download references

Author information

Affiliations

  1. N. Goormaghtigh Instituut voor Pathologische Ontleedkunde, Akademisch Ziekenhuis, Blok A, De Pintelaan 185, B-9000, Gent, Belgium

    Jozef Quatacker

Authors
  1. Jozef Quatacker
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Quatacker, J. Alterations in the sialic acid content of the rat glomerular filter in aminonucleoside nephrosis. Virchows Archiv B Cell Pathol 50, 237 (1986). https://doi.org/10.1007/BF02889904

Download citation

  • Received:

  • Accepted:

  • DOI: https://doi.org/10.1007/BF02889904

Key words

  • Aminonucleoside nephrosis
  • Sialic acid
  • Glomerulus
  • Basement membrane
  • Proteinuria
  • Anionic charges