Skip to main content
International Journal of Experimental Pathology logoLink to International Journal of Experimental Pathology
. 1993 Dec;74(6):553–560.

Suppression of development of anti-nuclear antibody and glomerulonephritis in NZB x NZWF1 mice by persistent infection with lactic dehydrogenase virus: possible involvement of superoxide anion as a progressive effector.

T Hayashi 1, Y Noguchi 1, Y Kameyama 1
PMCID: PMC2002257  PMID: 8292553

Abstract

The development of anti-nuclear antibody (ANA) and glomerulonephritis (GN) in autoimmune NZB x NZWF1 mice was suppressed by persistent lactic dehydrogenase virus (LDV) infection. This observation was used to study a possible pathogenetic role for the toxic oxygen radical, superoxide anion (O2-), in the progression of ANA and GN. Compared to macrophages from NZB x NZWF1 mice with LDV infection, macrophages from uninfected NZB x NZWF1 mice exhibited an age-related and drastic increase in O2- production in association with the development of the ANA and GN (representing the late stage of disease). NZB x NZWF1 mice with or without LDV infection were then given the O2- scavenger superoxide dismutase (SOD) during the late stage of the disease. Treatment of uninfected NZB x NZWF1 mice with SOD (10,000 units/mouse/day for 3 weeks) protected animals from the development of ANA and GN. SOD treatment also suppressed the development of the lesions in NZB x NZWF1 mice with LDV infection. Our findings suggest that O2- may, at least in part, contribute to the development of ANA and GN in the late stage of disease, and that decreased O2- production in NZB x NZWF1 mice with LDV infection may be responsible for the suppression of the development of ANA and GN in the late stage of the disease.

Full text

PDF
553

Images in this article

Selected References

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

  1. Dixon F. J. ARA Kunkel memorial lecture. Murine lupus. A model for human autoimmunity. Arthritis Rheum. 1985 Oct;28(10):1081–1088. doi: 10.1002/art.1780281002. [DOI] [PubMed] [Google Scholar]
  2. Emerit I., Cerutti P. A. Tumor promoter phorbol 12-myristate 13-acetate induces a clastogenic factor in human lymphocytes. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7509–7513. doi: 10.1073/pnas.79.23.7509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Emerit I., Levy A., Michelson A. M. Effect of superoxide dismutase on the chromosomal instability of New Zealand black mice. Cytogenet Cell Genet. 1981;30(2):65–69. doi: 10.1159/000131592. [DOI] [PubMed] [Google Scholar]
  4. Farber J. L., Kyle M. E., Coleman J. B. Mechanisms of cell injury by activated oxygen species. Lab Invest. 1990 Jun;62(6):670–679. [PubMed] [Google Scholar]
  5. Goldstein I. M., Kaplan H. B., Edelson H. S., Weissmann G. Ceruloplasmin. A scavenger of superoxide anion radicals. J Biol Chem. 1979 May 25;254(10):4040–4045. [PubMed] [Google Scholar]
  6. Hayashi T., Mori I., Yamamoto H. Lactic dehydrogenase virus infection prevents development of anti-nuclear antibody in (NZB x NZW)F1 mice; role of prostaglandin E2 and macrophage Ia antigen expression. Int J Exp Pathol. 1992 Oct;73(5):593–601. [PMC free article] [PubMed] [Google Scholar]
  7. Hayashi T., Onodera T., Yamamoto H. Detection of the binding of IgG2a and IgG2b on the surface of macrophages from mice chronically infected with lactic dehydrogenase virus. J Comp Pathol. 1992 Jul;107(1):35–40. doi: 10.1016/0021-9975(92)90093-a. [DOI] [PubMed] [Google Scholar]
  8. Hayashi T., Ozaki M., Ami Y., Onodera T., Yamamoto H. Increased superoxide anion release by peritoneal macrophages in mice with a chronic infection of lactic dehydrogenase virus. J Comp Pathol. 1992 Jan;106(1):93–98. doi: 10.1016/0021-9975(92)90073-4. [DOI] [PubMed] [Google Scholar]
  9. Hayashi T., Salata K., Kingman A., Notkins A. L. Regulation of enzyme levels in the blood. Influence of environmental and genetic factors on enzyme clearance. Am J Pathol. 1988 Sep;132(3):503–511. [PMC free article] [PubMed] [Google Scholar]
  10. Izui S., McConahey P. J., Theofilopoulos A. N., Dixon F. J. Association of circulating retroviral gp70-anti-gp70 immune complexes with murine systemic lupus erythematosus. J Exp Med. 1979 May 1;149(5):1099–1116. doi: 10.1084/jem.149.5.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Maruyama N., Furukawa F., Nakai Y., Sasaki Y., Ohta K., Ozaki S., Hirose S., Shirai T. Genetic studies of autoimmunity in New Zealand mice. IV. Contribution of NZB and NZW genes to the spontaneous occurrence of retroviral gp70 immune complexes in (NZB X NZW)F1 hybrid and the correlation to renal disease. J Immunol. 1983 Feb;130(2):740–746. [PubMed] [Google Scholar]
  13. Oldham K. T., Guice K. S., Ward P. A., Johnson K. J. The role of oxygen radicals in immune complex injury. Free Radic Biol Med. 1988;4(6):387–397. doi: 10.1016/0891-5849(88)90090-1. [DOI] [PubMed] [Google Scholar]
  14. Oldstone M. B., Dixon F. J. Inhibition of antibodies to nuclear antigen and to DNA in New Zealand mice infected with lactate dehydrogenase virus. Science. 1972 Feb 18;175(4023):784–786. doi: 10.1126/science.175.4023.784. [DOI] [PubMed] [Google Scholar]
  15. Rokutan K., Hosokawa T., Nakamura K., Koyama K., Aoike A., Kawai K. Increased superoxide anion production and glutathione peroxidase activity in peritoneal macrophages from autoimmune-prone MRL/Mp-Ipr/lpr mice. Int Arch Allergy Appl Immunol. 1988;87(2):113–119. doi: 10.1159/000234660. [DOI] [PubMed] [Google Scholar]
  16. Rowson K. E., Mahy B. W. Lactate dehydrogenase-elevating virus. J Gen Virol. 1985 Nov;66(Pt 11):2297–2312. doi: 10.1099/0022-1317-66-11-2297. [DOI] [PubMed] [Google Scholar]
  17. Schraufstätter I., Hyslop P. A., Jackson J. H., Cochrane C. G. Oxidant-induced DNA damage of target cells. J Clin Invest. 1988 Sep;82(3):1040–1050. doi: 10.1172/JCI113660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tokado H., Yumura W., Shiota J., Hirose S., Sato H., Shirai T. Lupus nephritis in autoimmune-prone NZB x NZW F1 mice and mechanisms of transition of the glomerular lesions. Acta Pathol Jpn. 1991 Jan;41(1):1–11. [PubMed] [Google Scholar]
  19. Yoshida H., Kohno A., Ohta K., Hirose S., Maruyama N., Shirai T. Genetic studies of autoimmunity in New Zealand mice. III. Associations among anti-DNA antibodies, NTA, and renal disease in (NZB x NZW)F1 x NZW backcross mice. J Immunol. 1981 Aug;127(2):433–437. [PubMed] [Google Scholar]
  20. Yoshiki T., Mellors R. C., Strand M., August J. T. The viral envelope glycoprotein of murine leukemia virus and the pathogenesis of immune complex glomerulonephritis of New Zealand mice. J Exp Med. 1974 Oct 1;140(4):1011–1027. doi: 10.1084/jem.140.4.1011. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from International Journal of Experimental Pathology are provided here courtesy of Wiley

RESOURCES