Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Feb;95(2):327–332. doi: 10.1111/j.1365-2249.1994.tb06532.x

Proteinuria induced by anti-dipeptidyl peptidase IV (gp108); role of circulating and glomerular antigen.

Y Natori 1, N Shindo 1, Y Natori 1
PMCID: PMC1534929  PMID: 7905795

Abstract

Massive proteinuria is induced in rats by administration of rabbit antibody to dipeptidyl peptidase IV (DPPIV, gp108), a glycoprotein present on glomerular cell membranes and in serum. This study was undertaken to know which antigen, glomerular or serum DPPIV, is responsible for forming immune complex in glomeruli and development of proteinuria. An i.p. injection of the antibody resulted in a rapid decrease of serum DPPIV and a gradual increase of rabbit IgG deposited along glomerular capillary wall for 4-8 h. Abnormal proteinuria appeared within 8 h, peaked on day 2 (> 200 mg/24 h) and then declined. An increase of urinary protein and glomerular deposition of IgG also occurred, when the antibody was injected into serum DPPIV-depleted rats that had received preinjection of anti-DPPIV antibody. These results suggest that proteinuria is induced by direct binding of anti-DPPIV antibody to the membrane antigen of glomerular cells.

Full text

PDF
332

Images in this article

329Fig. 4
on p.329
330Fig. 5
on p.330
330Fig. 6
on p.330

Selected References

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

  1. 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]
  2. Bagchus W. M., Hoedemaeker P. J., Slegers J. F., Bakker W. W. The specificity of nephritogenic antibodies. V. Glomerular localization of anti-GP 330 and anti-GP 90 antibodies present in passive Heymann serum. Br J Exp Pathol. 1988 Dec;69(6):855–864. [PMC free article] [PubMed] [Google Scholar]
  3. Bauvois B. A collagen-binding glycoprotein on the surface of mouse fibroblasts is identified as dipeptidyl peptidase IV. Biochem J. 1988 Jun 15;252(3):723–731. doi: 10.1042/bj2520723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bruijn J. A., Hogendoorn P. C., Hoedemaeker P. J., Fleuren G. J. The extracellular matrix in pathology. J Lab Clin Med. 1988 Feb;111(2):140–149. [PubMed] [Google Scholar]
  5. Camussi G., Brentjens J. R., Noble B., Kerjaschki D., Malavasi F., Roholt O. A., Farquhar M. G., Andres G. Antibody-induced redistribution of Heymann antigen on the surface of cultured glomerular visceral epithelial cells: possible role in the pathogenesis of Heymann glomerulonephritis. J Immunol. 1985 Oct;135(4):2409–2416. [PubMed] [Google Scholar]
  6. Chatelet F., Brianti E., Ronco P., Roland J., Verroust P. Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. I. Renal distribution. Am J Pathol. 1986 Mar;122(3):500–511. [PMC free article] [PubMed] [Google Scholar]
  7. Couser W. G. Mechanisms of glomerular injury in immune-complex disease. Kidney Int. 1985 Sep;28(3):569–583. doi: 10.1038/ki.1985.167. [DOI] [PubMed] [Google Scholar]
  8. Couser W. G., Steinmuller D. R., Stilmant M. M., Salant D. J., Lowenstein L. M. Experimental glomerulonephritis in the isolated perfused rat kidney. J Clin Invest. 1978 Dec;62(6):1275–1287. doi: 10.1172/JCI109248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feenstra K., van den Lee R., Greben H. A., Arends A., Hoedemaeker P. J. Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. I. The natural history: a histologic and immunohistologic study at the light microscopic and the ultrastructural level. Lab Invest. 1975 Feb;32(2):235–242. [PubMed] [Google Scholar]
  10. Glassock R. J., Edgington T. S., Watson J. I., Dixon F. J. Autologous immune complex nephritis induced with renal tubular antigen. II. The pathogenetic mechanism. J Exp Med. 1968 Mar 1;127(3):573–588. doi: 10.1084/jem.127.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HEYMANN W., HACKEL D. B., HARWOOD S., WILSON S. G., HUNTER J. L. Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions. Proc Soc Exp Biol Med. 1959 Apr;100(4):660–664. doi: 10.3181/00379727-100-24736. [DOI] [PubMed] [Google Scholar]
  12. Hanski C., Huhle T., Gossrau R., Reutter W. Direct evidence for the binding of rat liver DPP IV to collagen in vitro. Exp Cell Res. 1988 Sep;178(1):64–72. doi: 10.1016/0014-4827(88)90378-3. [DOI] [PubMed] [Google Scholar]
  13. Hanski C., Huhle T., Reutter W. Involvement of plasma membrane dipeptidyl peptidase IV in fibronectin-mediated adhesion of cells on collagen. Biol Chem Hoppe Seyler. 1985 Dec;366(12):1169–1176. doi: 10.1515/bchm3.1985.366.2.1169. [DOI] [PubMed] [Google Scholar]
  14. Hixson D. C., DeLourdes Ponce M., Allison J. P., Walborg E. F., Jr Cell surface expression by adult rat hepatocytes of a non-collagen glycoprotein present in rat liver biomatrix. Exp Cell Res. 1984 Jun;152(2):402–414. doi: 10.1016/0014-4827(84)90641-4. [DOI] [PubMed] [Google Scholar]
  15. Hong W. J., Petell J. K., Swank D., Sanford J., Hixson D. C., Doyle D. Expression of dipeptidyl peptidase IV in rat tissues is mainly regulated at the mRNA levels. Exp Cell Res. 1989 May;182(1):256–266. doi: 10.1016/0014-4827(89)90296-6. [DOI] [PubMed] [Google Scholar]
  16. Hopsu-Havu V. K., Ekfors T. O. Distribution of a dipeptide naphthylamidase in rat tissues and its localisation by using diazo coupling and labeled antibody techniques. Histochemie. 1969;17(1):30–38. doi: 10.1007/BF00306327. [DOI] [PubMed] [Google Scholar]
  17. Kerjaschki D., Farquhar M. G. Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats. J Exp Med. 1983 Feb 1;157(2):667–686. doi: 10.1084/jem.157.2.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kerjaschki D., Miettinen A., Farquhar M. G. Initial events in the formation of immune deposits in passive Heymann nephritis. gp330-anti-gp330 immune complexes form in epithelial coated pits and rapidly become attached to the glomerular basement membrane. J Exp Med. 1987 Jul 1;166(1):109–128. doi: 10.1084/jem.166.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Mendrick D. L., Rennke H. G. Induction of proteinuria in the rat by a monoclonal antibody against SGP-115/107. Kidney Int. 1988 Apr;33(4):818–830. doi: 10.1038/ki.1988.73. [DOI] [PubMed] [Google Scholar]
  21. Nagatsu T., Hino M., Fuyamada H., Hayakawa T., Sakakibara S. New chromogenic substrates for X-prolyl dipeptidyl-aminopeptidase. Anal Biochem. 1976 Aug;74(2):466–476. doi: 10.1016/0003-2697(76)90227-x. [DOI] [PubMed] [Google Scholar]
  22. Naruse T., Fukasawa T., Hirokawa N., Oike S., Miyakawa Y. The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen. J Exp Med. 1976 Nov 2;144(5):1347–1362. doi: 10.1084/jem.144.5.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Natori Y., Hayakawa I., Shibata S. Identification of gp108, a pathogenic antigen of passive Heymann nephritis, as dipeptidyl peptidase IV. Clin Exp Immunol. 1987 Nov;70(2):434–439. [PMC free article] [PubMed] [Google Scholar]
  24. Natori Y., Hayakawa I., Shibata S. Passive Heymann nephritis with acute and severe proteinuria induced by heterologous antibody against renal tubular brush border glycoprotein gp108. Lab Invest. 1986 Jul;55(1):63–70. [PubMed] [Google Scholar]
  25. Natori Y., Hayakawa I., Shibata S. The detection and characterization of renal brush border antigen (gp108) in various rat tissues. Clin Exp Immunol. 1987 Jan;67(1):135–141. [PMC free article] [PubMed] [Google Scholar]
  26. Natorio Y., Hayakawa I., Shibata S. Role of dipeptidyl peptidase IV (gp 108) in passive Heymann nephritis. Use of dipeptidyl peptidase IV-deficient rats. Am J Pathol. 1989 Feb;134(2):405–410. [PMC free article] [PubMed] [Google Scholar]
  27. Van Damme B. J., Fleuren G. J., Bakker W. W., Vernier R. L., Hoedemaeker P. J. Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. V. Fixed glomerular antigens in the pathogenesis of heterologous immune complex glomerulonephritis. Lab Invest. 1978 Apr;38(4):502–510. [PubMed] [Google Scholar]
  28. Walborg E. F., Jr, Tsuchida S., Weeden D. S., Thomas M. W., Barrick A., McEntire K. D., Allison J. P., Hixson D. C. Identification of dipeptidyl peptidase IV as a protein shared by the plasma membrane of hepatocytes and liver biomatrix. Exp Cell Res. 1985 Jun;158(2):509–518. doi: 10.1016/0014-4827(85)90474-4. [DOI] [PubMed] [Google Scholar]
  29. van Leer E. H., Bruijn J. A., Prins F. A., Hoedemaeker P. J., de Heer E. Redistribution of glomerular dipeptidyl peptidase type IV in experimental lupus nephritis. Demonstration of decreased enzyme activity at the ultrastructural level. Lab Invest. 1993 May;68(5):550–556. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES