Summary
Cationic antigens have been observed to bind with the negatively charged glomerular basement membrane (GBM). Using the cationic reagent polyethyleneimine (PEI), the distribution of glomerular anionic sites was evaluated ultrastructurally in the early stage (2 h-day 7) of cationic antigen mediated in-situ immune complex formation type glomerulonephritis (GN) in the rat. — Renal perfusion via the renal artery with 100 μg of cationized human IgG (pl>9.5), followed by the i.v. injection of specific antibodies, led to an initial increase in urinary albumin excretion, subsequent massive globulinuria and the formation of numerous subepithelial deposits on day 7. — The most striking alteration in glomerular anionic sites was observed on the epithelial cell surface coat; the PEI deposition on the epithelial cell surface was almost identical to that in control glomeruli at 2 and 4 h after the induction of GN; thereafter, on day 7, a broad loss of anionic sites was obseryed on flattened epithelial foot processes. In contrast, fixed anionic sites of the laminae rarae of the GBM showed no apparent alterations in the distribution and number from 2 h to day 7 and did not disappear even in the lamina rara externa adjacent to subepithelial deposits. — These findings not only show that fixed anionic sites of the GBM, in contrast to the rapid decrease in those of the epithelial cell surface, are not completely neutralized or destroyed even in GN, in which cationic antigen participates in the in-situ formation of GBM-deposits. This also indicates that initial impairment of the charge-selective barrier of the GBM by the in-situ interaction between cationic antigen and antibody, is followed by the disfunction of the size-selective permselectivity of the GBM, ultimately causing massive proteinuria.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Barnes JL, Radnik RA, Gilchrist EP, Venkatachalam MA (1983) Size and charge selective permeability defects induced in glomerular basement membrane by a polycation [abstract]. Kidney Int 23:179
Batsford SR, Takamiya H, Vogt A (1980a) A model of in situ immune complex glomerulonephritis in the rat employing cationized ferritin. Clin Nephrol 14:211–216
Batsford SR, Oite T, Takamiya H, Vogt A (1980b) Anionic binding sites in the glomerular basement membrane: possible role in the pathogenesis of immune complex glomerulonephritis. Renal Physiol 3:336–340
Batsford SR, Sasaki M, Takamiya H, Vogt A (1983) Cationic macromolecule-induced nephrotic syndrome in rabbits. Lack of immune complex involvement. Lab Invest 49:260–269
Caulfield JP, Farquhar MG (1978) Loss of anionic sites from the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest 39:505–512
Danon D, Goldstein Y, Marikovsky Y, Skutelsky E (1972) Use of cationized ferritin as a label of negative charges on cell surfaces. J Ultrastruct Res 38:500–510
Farquhar MG (1980) Role of the basement membrane in glomerular filtration: Results obtained with electron-dense tracers. In: Functional ultrastructure of the kidney. Academic Press, New York, p 31
Hunsicker LG, Shearer TP (1979) A model of acute reversible proteinuria induced by polycation infusion [abstract]. Kidney Int 16:783
Hunsicker LG, Shearer TP, Shaffer SJ (1981) Acute reversible proteinuria induced by infusion of the polycation hexadimethrine. Kidney Int 20:7–17
Hunsicker LG, Shaffer SJ, Bertolatus JA (1983) Hexadimethrine (HDM) induced proteinuria: lag between glomerular HDM binding and proteinuria [abstract]. Kidney Int 20:183
Jones DB (1969) Mucosubstances of the glomerulus. Lab Invest 21:119–125
Kanwar YS, Farquhar MG (1979a) Presence of heparan sulfate in the glomerular basement membrane. Proc Natl Acad Sci USA 76:1303–1307
Kanwar YS, Farquhar MG (1979b) Anionic sites in the glomerular basement membrane. In vivo and in vitro localization to the laminae rarae by cationic probes. J Cell Biol 81:137–153
Kanwar YS, Farquhar MG (1979c) Isolation of glycosaminoglycans (heparan sulfate) from glomerular basement membrane. Proc Natl Acad Sci USA 76:4493–4497
Michael AF, Blau E, Vienier RL (1970) Glomerular polyanion. Alteration in aminonucleoside nephrosis. Lab Invest 23:649–657
Oite T, Batsford SR, Mihatsch MJ, Takamiya H, Vogt A (1982) Quantitative studies of in situ immune complex glomerulonephritis in the rat by planted cationized antigen. J Exp Med 155:460–474
Oite T, Shimizu F, Kihara I, Batsford SR, Vogt A (1983) An active model of immune complex glomerulonephritis in the rat employing cationized antigen. Am J Pathol 112:185–194
Rennke HG, Cotran RS, Venkatachalam MA (1975) Role of molecular charges in glomerular permeability. Tracer studies with cationized ferritin. J Cell Biol 67:638–646
Schurer JW, Kalicharan D, Hoedemaeker PhJ, Molenaar I (1978) Demonstration of anionic sites in basement membrane and in collagen fibrils. J Histochem Cytochem 26:688–689
Schurer JW, Fleuren GJ, Hoedemaker PhJ, Molenaaer I (1980) A macromolecular model of the glomerular basement membrane. In: Functional ultrastructure of the kidney. Academic Press, New York, p 105
Seiler MW, Venkatachalam MA, Cotran RS (1975) Glomerular epithelium: structural alterations induced by polycations. Science 189:390–393
Seiler MW, Rennke HG, Venkatachalam MA, Cotran RS (1977) Pathogenesis of polycation-induced alterations (“fusion”) of glomerular epithelium. Lab Invest 36:48–61
Seno S, Tsujii T, Ono T, Ukita S (1983) Cationic cacodylate iron colloid for the detection of anionic sites on cell surface and the histochemical stain of acid mucopolysaccharides. Histochemistry 78:27–31
Suzuki Y, Maesawa A, Matsui K, Oite T, Koda Y, Arakawa M (1983) Alteration of glomerular anionic sites by the development of subepithelial deposits in experimental glomerulonephritis in the rat. Virchows Arch [Cell Pathol] 44:209–222
Vehaskari VM, Root ER, Germuth FG Jr, Robson AM (1982) Glomerular charge and urinary protein excretion: effects of systemic and intrarenal polycation infusion in the rat [abstract]. Kidney Int 22:127
Vogt A, Schmidt U, Takamiya H, Batsford SR (1980) In situ immune complex nephritis and basic proteins, Proc EDTA. Pitman, London. Medical Publishing Co Ltd, tumbridge Wells, Kent 17:613–620
Vogt A, Rohrbach R, Shimizu F, Takamiya H, Batsford S (1982) Interaction of cationized antigen with rat glomerular basement membrane: In situ immune complex formation. Kidney Int 22:27–35
Vogt A, Batsford S, Rodriguez-Iturbe B, Garcia R (1983) Cationic antigens in poststreptococcal glomerulonephritis. Clin Nephrol 20:271–279
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Suzuki, Y., Maruyama, Y., Arakawa, M. et al. Preservation of fixed anionic sites in the GBM in the acute proteinuric phase of cationic antigen mediated in-situ immune complex glomerulonephritis in the rat. Histochemistry 81, 243–246 (1984). https://doi.org/10.1007/BF00495634
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00495634