Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1988 Jan;130(1):103–111.

Characterization of renal injury initiated by immunization of rats with heparan sulfate.

C K Abrass 1, A H Cohen 1
PMCID: PMC1880534  PMID: 2962503

Abstract

To investigate the role of antibody to heparan sulfate (HS) in the development of glomerular injury, male Lewis rats were immunized with HS and compared with unimmunized controls. In HS-immunized rats circulating antibodies that bound to renal basement membranes, an increase in serum creatinine (0.8 mg/dl versus 0.6 in controls P less than 0.01), and a 40% decline in creatinine clearance developed. In no animal did abnormal proteinuria develop. By histologic examination there was glomerular and interstitial capillary engorgement with erythrocytes, modest infiltration by polymorphonuclear leukocytes, and no proliferation of intrinsic glomerular cells. Immunofluorescence microscopy demonstrated deposits of rat IgG along the glomerular basement membrane. Bowman's capsule, and peritubular capillaries. Electron-microscopic examination revealed capillary engorgement with erythrocytes that appeared adherent to each other and contained entrapped areas of rarefied material. These observations demonstrate that binding of antibody to HS in the glomerulus induces a mild inflammatory reaction and a reduction in glomerular filtration rate, but no abnormal proteinuria.

Full text

PDF
103

Images in this article

107Figure 1
on p.107
108Figure 2
on p.108
108Figure 3
on p.108
109Figure 4
on p.109

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrahamson D. R., Caulfield J. P. Proteinuria and structural alterations in rat glomerular basement membranes induced by intravenously injected anti-laminin immunoglobulin G. J Exp Med. 1982 Jul 1;156(1):128–145. doi: 10.1084/jem.156.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abrahamson D. R., Hein A., Caulfield J. P. Laminin in glomerular basement membranes of aminonucleoside nephrotic rats. Increased proteinuria induced by antilaminin immunoglobulin G. Lab Invest. 1983 Jul;49(1):38–47. [PubMed] [Google Scholar]
  3. Abrass C. K., Border W. A., Glassock R. J. Circulating immune complexes in rats with autologous immune complex nephritis. Lab Invest. 1980 Jul;43(1):18–27. [PubMed] [Google Scholar]
  4. Abrass C. K. Evaluation of sequential glomerular eluates from rats with Heymann nephritis. J Immunol. 1986 Jul 15;137(2):530–535. [PubMed] [Google Scholar]
  5. Cappelletti R., Del Rosso M., Vannucchi S., Cella C., Fibbi G., Chiarugi V. P. Involvement of modulation of cell coat glycosaminoglycans in guinea pig peritoneal macrophage activity. J Reticuloendothel Soc. 1980 Apr;27(4):383–391. [PubMed] [Google Scholar]
  6. Couser W. G., Baker P. J., Adler S. Complement and the direct mediation of immune glomerular injury: a new perspective. Kidney Int. 1985 Dec;28(6):879–890. doi: 10.1038/ki.1985.214. [DOI] [PubMed] [Google Scholar]
  7. Dietrich C. P., Montes de Oca H. Surface sulfated mucopolysaccharides of primary and permanent mammalian cell lines. Biochem Biophys Res Commun. 1978 Feb 28;80(4):805–812. doi: 10.1016/0006-291x(78)91316-5. [DOI] [PubMed] [Google Scholar]
  8. Glimelius B., Norling B., Westermark B., Wasteson A. Composition and distribution of glycosaminoglycans in cultures of human normal and malignant glial cells. Biochem J. 1978 Jun 15;172(3):443–456. doi: 10.1042/bj1720443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hassell J. R., Robey P. G., Barrach H. J., Wilczek J., Rennard S. I., Martin G. R. Isolation of a heparan sulfate-containing proteoglycan from basement membrane. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4494–4498. doi: 10.1073/pnas.77.8.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. KRAKOWER C. A., GREENSPON S. A. Localization of the nephrotoxic antigen within the isolated renal glomerulus. AMA Arch Pathol. 1951 Jun;51(6):629–639. [PubMed] [Google Scholar]
  11. Kanwar Y. S., Farquhar M. G. Presence of heparan sulfate in the glomerular basement membrane. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1303–1307. doi: 10.1073/pnas.76.3.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kanwar Y. S., Linker A., Farquhar M. G. Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion. J Cell Biol. 1980 Aug;86(2):688–693. doi: 10.1083/jcb.86.2.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kanwar Y. S., Rosenzweig L. J. Altered glomerular permeability as a result of focal detachment of the visceral epithelium. Kidney Int. 1982 Apr;21(4):565–574. doi: 10.1038/ki.1982.63. [DOI] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Lerner R. A., Glassock R. J., Dixon F. J. The role of anti-glomerular basement membrane antibody in the pathogenesis of human glomerulonephritis. J Exp Med. 1967 Dec 1;126(6):989–1004. doi: 10.1084/jem.126.6.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Makino H., Gibbons J. T., Reddy M. K., Kanwar Y. S. Nephritogenicity of antibodies to proteoglycans of the glomerular basement membrane--I. J Clin Invest. 1986 Jan;77(1):142–156. doi: 10.1172/JCI112269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miettinen A., Stow J. L., Mentone S., Farquhar M. G. Antibodies to basement membrane heparan sulfate proteoglycans bind to the laminae rarae of the glomerular basement membrane (GBM) and induce subepithelial GBM thickening. J Exp Med. 1986 May 1;163(5):1064–1084. doi: 10.1084/jem.163.5.1064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Murphy-Ullrich J. E., Oberley T. D., Mosher D. F. Glomerular and vascular injury in mice following immunization with heterologous and autologous fibronectin. Virchows Arch B Cell Pathol Incl Mol Pathol. 1982;39(3):305–321. doi: 10.1007/BF02892857. [DOI] [PubMed] [Google Scholar]
  19. Rennke H. G., Cotran R. S., Venkatachalam M. A. Role of molecular charge in glomerular permeability. Tracer studies with cationized ferritins. J Cell Biol. 1975 Dec;67(3):638–646. doi: 10.1083/jcb.67.3.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SCHILLER S., SLOVER G. A., DORFMAN A. A method for the separation of acid mucopolysaccharides: its application to the isolation of heparin from the skin of rats. J Biol Chem. 1961 Apr;236:983–987. [PubMed] [Google Scholar]
  21. Ts'ao C. H., Eisenstein R., Schumacher B. Effect of an aortic proteoglycan on platelet aggregation and thrombin time: plasma requirement and active moieties (39898). Proc Soc Exp Biol Med. 1977 Oct;156(1):162–167. doi: 10.3181/00379727-156-39898. [DOI] [PubMed] [Google Scholar]
  22. UNANUE E. R., DIXON F. J. EXPERIMENTAL GLOMERULONEPHRITIS. V. STUDIES ON THE INTERACTION OF NEPHROTOXIC ANTIBODIES WITH TISSUE OF THE RAT. J Exp Med. 1965 May 1;121:697–714. doi: 10.1084/jem.121.5.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Van Pelt L. F. Ketamine and xylazine for surgical anesthesia in rats. J Am Vet Med Assoc. 1977 Nov 1;171(9):842–844. [PubMed] [Google Scholar]
  24. Vijayagopal P., Radhakrishnamurthy B., Srinivasan S. R., Berenson G. S. Studies of biologic properties of proteoglycans from bovine aorta. Lab Invest. 1980 Feb;42(2):190–196. [PubMed] [Google Scholar]
  25. Vijayagopal P., Srinivasan S. R., Radhakrishnamurthy B., Berenson G. S. Hemostatic properties and serum lipoprotein binding of a heparan sulfate proteoglycan from bovine aorta. Biochim Biophys Acta. 1983 Jul 5;758(1):70–83. doi: 10.1016/0304-4165(83)90011-9. [DOI] [PubMed] [Google Scholar]
  26. Wieslander J., Bygren P., Heinegård D. Antiglomerular basement membrane antibody: antibody specificity in different forms of glomerulonephritis. Kidney Int. 1983 Jun;23(6):855–861. doi: 10.1038/ki.1983.106. [DOI] [PubMed] [Google Scholar]
  27. Wieslander J., Langeveld J., Butkowski R., Jodlowski M., Noelken M., Hudson B. G. Physical and immunochemical studies of the globular domain of type IV collagen. Cryptic properties of the Goodpasture antigen. J Biol Chem. 1985 Jul 15;260(14):8564–8570. [PubMed] [Google Scholar]
  28. Woodroffe A. J., Wilson C. B. An evaluation of elution techniques in the study of immune complex glomerulonephritis. J Immunol. 1977 May;118(5):1788–1794. [PubMed] [Google Scholar]
  29. Yoshioka K., Kleppel M., Fish A. J. Analysis of nephritogenic antigens in human glomerular basement membrane by two-dimensional gel electrophoresis. J Immunol. 1985 Jun;134(6):3831–3837. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES