Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1983 Sep;53(3):562–572.

Tubulointerstitial nephritis in rabbits challenged with homologous Tamm-Horsfall protein: the role of endotoxin.

E S Berke, A R Mayrer, P Miniter, V T Andriole
PMCID: PMC1535638  PMID: 6616957

Abstract

Tubulointerstitial nephritis developed in 25 of 34 (74%) rabbits challenged intravenously for 2-20 weeks with adjuvant and endotoxin free homologous Tamm-Horsfall protein (THP). Lesions were characterized by focal mononuclear cellular infiltrates and microscopic scarring localized to distal nephron segments identified as thick ascending limb of the loop of Henle. Interstitial deposits of THP were found in the kidneys of more severely affected rabbits and metabolic studies demonstrated transient polyuria and tubular dysfunction. Elevations in serum IgG antibody against THP were detected in seven of 34 challenged rabbits. Tubulointerstitial nephritis was found in six of the seven rabbits with elevated antibody as well as in 19 of 27 rabbits without elevated antibody. By contrast, peripheral lymphocytes from eight of 13 rabbits with tubulointerstitial nephritis were cytotoxic against target fibroblasts in the presence of THP as compared to none of eight age matched challenged or unchallenged rabbits with normal kidneys. The presence or absence of endotoxin in vitro did not influence determinations of antibody- or lymphocyte-mediated cytotoxicity. These observations suggest that the tubulointerstitial nephritis which develops in rabbits challenged with THP is primarily the result of cell-mediated immune responses directed against THP, and does not require the presence of endotoxin in the challenge solution, or serum IgG antibodies directed against THP.

Full text

PDF
562

Images in this article

Selected References

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

  1. Bailey R. R. The relationship of vesico-ureteric reflux to urinary tract infection and chronic pyelonephritis-reflux nephropathy. Clin Nephrol. 1973 May-Jun;1(3):132–141. [PubMed] [Google Scholar]
  2. Bhagavan B. S., Wenk R. E., Dutta D. Pathways of urinary backflow in obstructive uropathy. Demonstration by pigmented gelatin injection and Tamm-Horsfall uromucoprotein markers. Hum Pathol. 1979 Nov;10(6):669–683. doi: 10.1016/s0046-8177(79)80111-2. [DOI] [PubMed] [Google Scholar]
  3. Chester T. J., de Clercq E., Merigan T. C. Effect of Separate and Combined Injections of Poly rI: Poly rC and Endotoxin on Reticulo-endothelial Activity, Interferon, and Antibody Production in the Mouse. Infect Immun. 1971 Apr;3(4):516–520. doi: 10.1128/iai.3.4.516-520.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Courtice F. C., Gunton R. W. The determination of blood volume by the carbon monoxide and dye (T-1824) methods in rabbits. J Physiol. 1949 Jun 15;108(4):405–417. doi: 10.1113/jphysiol.1949.sp004344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Elin R. J., Robinson R. A., Levine A. S., Wolff S. M. Lack of clinical usefulness of the limulus test in the diagnosis of endotoxemia. N Engl J Med. 1975 Sep 11;293(11):521–524. doi: 10.1056/NEJM197509112931102. [DOI] [PubMed] [Google Scholar]
  6. Fasth A., Ahlstedt S., Hanson L. A., Jann B., Jann K., Kaijser B. Cross-reactions between the Tamm-Horsfall glycoprotein and Escherichia coli. Int Arch Allergy Appl Immunol. 1980;63(3):303–311. doi: 10.1159/000232640. [DOI] [PubMed] [Google Scholar]
  7. Fasth A., Bengtsson U., Kaijser B., Wieslander J. Antibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults. Kidney Int. 1981 Oct;20(4):500–504. doi: 10.1038/ki.1981.167. [DOI] [PubMed] [Google Scholar]
  8. Fasth A., Hanson L. A., Asscher A. W. Autoantibodies to Tamm-Horsfall protein in detection of vesicoureteric reflux and kidney scarring. Arch Dis Child. 1977 Jul;52(7):560–562. doi: 10.1136/adc.52.7.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fournié G. J., Lambert P. H., Meischer P. A. Release of DNA in circulating blood and induction of anti-DNA antibodies after injection of bacterial lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1189–1206. doi: 10.1084/jem.140.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gery I., Gershon R. K., Waksman B. H. Potentiation of cultured mouse thymocyte responses by factors released by peripheral leucocytes. J Immunol. 1971 Dec;107(6):1778–1780. [PubMed] [Google Scholar]
  11. Hanson L. A., Fasth A., Jodal U. Autoantibodies to Tamm-Horsfall protein, a tool for diagnosing the level of urinary-tract infection. Lancet. 1976 Jan 31;1(7953):226–228. doi: 10.1016/s0140-6736(76)91342-8. [DOI] [PubMed] [Google Scholar]
  12. Hoyer J. R., Sisson S. P., Vernier R. L. Tamm-Horsfall glycoprotein: ultrastructural immunoperoxidase localization in rat kidney. Lab Invest. 1979 Aug;41(2):168–173. [PubMed] [Google Scholar]
  13. Hoyer J. R. Tubulointerstitial immune complex nephritis in rats immunized with Tamm-Horsfall protein. Kidney Int. 1980 Mar;17(3):284–292. doi: 10.1038/ki.1980.34. [DOI] [PubMed] [Google Scholar]
  14. Hutch J. A., Smith D. R. Sterile reflux: report of 24 cases. Urol Int. 1969;24(5):460–465. doi: 10.1159/000279643. [DOI] [PubMed] [Google Scholar]
  15. Izui S., Eisenberg R. A., Dixon F. J. IgM rheumatoid factors in mice injected with bacterial lipopolysaccharides. J Immunol. 1979 May;122(5):2096–2102. [PubMed] [Google Scholar]
  16. Lagrange P. H., Mackaness G. B., Miller T. E., Pardon P. Effects of bacterial lipopolysaccharide on the induction and expression of cell-mediated immunity. I. Depression of the afferent arc. J Immunol. 1975 Jan;114(1 Pt 2):442–446. [PubMed] [Google Scholar]
  17. Marier R., Fong E., Jansen M., Hodson C. J., Richards F., Andriole V. T. Antibody to Tamm-Horsfall protein in patients with urinary tract obstruction and vesicoureteral reflux. J Infect Dis. 1978 Dec;138(6):781–790. doi: 10.1093/infdis/138.6.781. [DOI] [PubMed] [Google Scholar]
  18. Marier R., Jansen M., Andriole V. T. A new method for measuring antibody using radiolabeled protein A1 in a solid-phase radioimmunoassay. J Immunol Methods. 1979;28(1-2):41–49. doi: 10.1016/0022-1759(79)90326-0. [DOI] [PubMed] [Google Scholar]
  19. Mayrer A. R., Kashgarian M., Ruddle N. H., Marier R., Hodson C. J., Richards F. F., Andriole V. T. Tubulointerstitial nephritis and immunologic responses to Tamm-Horsfall protein in rabbits challenged with homologous urine or Tamm-Horsfall protein. J Immunol. 1982 Jun;128(6):2634–2642. [PubMed] [Google Scholar]
  20. Mond J., Kim Y. T., Siskind G. W. Studies on the control of antibody synthesis. V. Effect of nonspecific modification of the magnitude of the immune response on the affinity of the antibody synthesized. J Immunol. 1974 Mar;112(3):1255–1263. [PubMed] [Google Scholar]
  21. NEUBERGER A., NIVEN J. S. F. Haemoglobin formation in rabbits. J Physiol. 1951 Feb;112(3-4):292–310. doi: 10.1113/jphysiol.1951.sp004530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Narayanan P. R., Kloehn D. B., Sundharadas G. Immune response to alloantigens in vitro, amplification of the development of cytotoxic T lymphocytes by lipopolysaccharide and polyadenylic:polyuridylic acid. J Immunol. 1978 Dec;121(6):2502–2508. [PubMed] [Google Scholar]
  23. Neilson E. G., Phillips S. M. Cell-mediated immunity in interstitial nephritis. II. T lymphocyte effector mechanisms in nephritic guinea pigs: analysis of the renotropic migration and cytotoxic response. J Immunol. 1979 Nov;123(5):2381–2385. [PubMed] [Google Scholar]
  24. Resnick J. S., Sisson S., Vernier R. L. Tamm-Horsfall protein. Abnormal localization in renal disease. Lab Invest. 1978 May;38(5):550–555. [PubMed] [Google Scholar]
  25. Salvatierra O., Jr, Kountz S. L., Belzer F. O. Primary vesicoureteral reflux and end-stage renal disease. JAMA. 1973 Dec 17;226(12):1454–1456. [PubMed] [Google Scholar]
  26. Sanford J. P. Urinary tract symptoms and infections. Annu Rev Med. 1975;26:485–498. doi: 10.1146/annurev.me.26.020175.002413. [DOI] [PubMed] [Google Scholar]
  27. Schenck J. R., Hargie M. P., Brown M. S., Ebert D. S., Yoo A. L., McIntire F. C. The enhancement of antibody formation by Escherichia coli lipopolysaccharide and detoxified derivatives. J Immunol. 1969 Jun;102(6):1411–1422. [PubMed] [Google Scholar]
  28. Sikri K. L., Foster C. L., MacHugh N., Marshall R. D. Localization of Tamm-Horsfall glycoprotein in the human kidney using immuno-fluorescence and immuno-electron microscopical techniques. J Anat. 1981 Jun;132(Pt 4):597–605. [PMC free article] [PubMed] [Google Scholar]
  29. Solez K., Heptinstall R. H. Intrarenal urinary extravasation with formation of venous polyps containing Tamm-Horsfall protein. J Urol. 1978 Feb;119(2):180–183. doi: 10.1016/s0022-5347(17)57428-5. [DOI] [PubMed] [Google Scholar]
  30. Whang H. Y., Neter E. Further studies on effect of endotoxin on antibody response of rabbit to common antigen of Enterobacteriaceae. J Immunol. 1967 May;98(5):948–957. [PubMed] [Google Scholar]
  31. Zager R. A., Cotran R. S., Hoyer J. R. Pathologic localization of Tamm-Horsfall protein in interstitial deposits in renal disease. Lab Invest. 1978 Jan;38(1):52–57. [PubMed] [Google Scholar]

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

RESOURCES