Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1995 Nov;4(6):444–451. doi: 10.1155/S0962935195000718

Abrogation of mercuric chloride-induced nephritis in the Brown Norway rat by treatment with antibodies against TNFα

A Molina 1, F Sánchez-Madrid 2, T Bricio 1, A Martín 1, E Escudero 1, V Alvarez 2, F Mampaso 1,✉
PMCID: PMC2365666  PMID: 18475678

Abstract

HgCl2 induces an autoimmune disease in the Brown Norway rat characterized by synthesis of autoantibodies (mainly, anti-GBM Abs), severe proteinuria and interstitial nephritis. Also, HgCl2- injected rats develop glomerular cell infiltrates consisting of ED1+ cells (monocyte/macrophage), starting on day 4 and reaching a maximum on day 8. Treatment with anti-TNF-α antiserum had preventative effects as it reduced the urinary protein levels to close to the normal range and also blocked the influx of inflammatory cells in the renal glomeruli and interstitium, but circulating anti-GBM and lineal glomerular IgG deposits were unmodified. In addition, whole isolated glomeruli from HgCl2-induced nephritis secreted TNF-α commencing on day 8, being maximally detected on day 11 and preceding, between 2 to 3 days, the development of proteinuria. The administration of anti-TNF-α antiserum or anti-α4 integrin mAb completely abrogated the synthesis of TNF-α in glomeruli isolated from the respective treated groups of animals, in addition to the proteinuria. Taken together our results confirm that TNF-α plays an important role in the induction and development of HgCl2-induced nephritis and highlights the pathogenic importance of the local release of TNF in those renal diseases in which prominent glomerular macrophage accumulation is a constant feature.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Affres H., Perez J., Hagege J., Fouqueray B., Kornprobst M., Ardaillou R., Baud L. Desferrioxamine regulates tumor necrosis factor release in mesangial cells. Kidney Int. 1991 May;39(5):822–830. doi: 10.1038/ki.1991.103. [DOI] [PubMed] [Google Scholar]
  2. Baud L., Oudinet J. P., Bens M., Noe L., Peraldi M. N., Rondeau E., Etienne J., Ardaillou R. Production of tumor necrosis factor by rat mesangial cells in response to bacterial lipopolysaccharide. Kidney Int. 1989 May;35(5):1111–1118. doi: 10.1038/ki.1989.98. [DOI] [PubMed] [Google Scholar]
  3. Bowman C., Mason D. W., Pusey C. D., Lockwood C. M. Autoregulation of autoantibody synthesis in mercuric chloride nephritis in the Brown Norway rat. I. A role for T suppressor cells. Eur J Immunol. 1984 May;14(5):464–470. doi: 10.1002/eji.1830140515. [DOI] [PubMed] [Google Scholar]
  4. Bowman C., Peters D. K., Lockwood C. M. Anti-glomerular basement membrane autoantibodies in the Brown Norway rat: detection by a solid-phase radioimmunoassay. J Immunol Methods. 1983 Jul 29;61(3):325–333. doi: 10.1016/0022-1759(83)90227-2. [DOI] [PubMed] [Google Scholar]
  5. Chin Y. H., Cai J. P., Johnson K. Lymphocyte adhesion to cultured Peyer's patch high endothelial venule cells is mediated by organ-specific homing receptors and can be regulated by cytokines. J Immunol. 1990 Dec 1;145(11):3669–3677. [PubMed] [Google Scholar]
  6. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  7. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  8. Hartung H. P. Immune-mediated demyelination. Ann Neurol. 1993 Jun;33(6):563–567. doi: 10.1002/ana.410330602. [DOI] [PubMed] [Google Scholar]
  9. Hruby Z. W., Shirota K., Jothy S., Lowry R. P. Antiserum against tumor necrosis factor-alpha and a protease inhibitor reduce immune glomerular injury. Kidney Int. 1991 Jul;40(1):43–51. doi: 10.1038/ki.1991.177. [DOI] [PubMed] [Google Scholar]
  10. Ju S. T., Ruddle N. H., Strack P., Dorf M. E., DeKruyff R. H. Expression of two distinct cytolytic mechanisms among murine CD4 subsets. J Immunol. 1990 Jan 1;144(1):23–31. [PubMed] [Google Scholar]
  11. Karniski L. P. Hg2+ and Cu+ are ionophores, mediating Cl-/OH- exchange in liposomes and rabbit renal brush border membranes. J Biol Chem. 1992 Sep 25;267(27):19218–19225. [PubMed] [Google Scholar]
  12. Mampaso F. M., Wilson C. B. Characterization of inflammatory cells in autoimmune tubulointerstitial nephritis in rats. Kidney Int. 1983 Mar;23(3):448–457. doi: 10.1038/ki.1983.41. [DOI] [PubMed] [Google Scholar]
  13. McMaster W. R., Williams A. F. Identification of Ia glycoproteins in rat thymus and purification from rat spleen. Eur J Immunol. 1979 Jun;9(6):426–433. doi: 10.1002/eji.1830090603. [DOI] [PubMed] [Google Scholar]
  14. Mulligan M. S., Johnson K. J., Todd R. F., 3rd, Issekutz T. B., Miyasaka M., Tamatani T., Smith C. W., Anderson D. C., Ward P. A. Requirements for leukocyte adhesion molecules in nephrotoxic nephritis. J Clin Invest. 1993 Feb;91(2):577–587. doi: 10.1172/JCI116237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mulligan M. S., Varani J., Dame M. K., Lane C. L., Smith C. W., Anderson D. C., Ward P. A. Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats. J Clin Invest. 1991 Oct;88(4):1396–1406. doi: 10.1172/JCI115446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Osborn L., Vassallo C., Benjamin C. D. Activated endothelium binds lymphocytes through a novel binding site in the alternately spliced domain of vascular cell adhesion molecule-1. J Exp Med. 1992 Jul 1;176(1):99–107. doi: 10.1084/jem.176.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pober J., Cotran R. S. What can be learned from the expression of endothelial adhesion molecules in tissues? Lab Invest. 1991 Mar;64(3):301–305. [PubMed] [Google Scholar]
  18. Postigo A. A., Sánchez-Mateos P., Lazarovits A. I., Sánchez-Madrid F., de Landázuri M. O. Alpha 4 beta 7 integrin mediates B cell binding to fibronectin and vascular cell adhesion molecule-1. Expression and function of alpha 4 integrins on human B lymphocytes. J Immunol. 1993 Sep 1;151(5):2471–2483. [PubMed] [Google Scholar]
  19. Pulido R., Elices M. J., Campanero M. R., Osborn L., Schiffer S., García-Pardo A., Lobb R., Hemler M. E., Sánchez-Madrid F. Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha 4 epitopes. J Biol Chem. 1991 Jun 5;266(16):10241–10245. [PubMed] [Google Scholar]
  20. Smith M. W., Phelps P. C., Trump B. F. Cytosolic Ca2+ deregulation and blebbing after HgCl2 injury to cultured rabbit proximal tubule cells as determined by digital imaging microscopy. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4926–4930. doi: 10.1073/pnas.88.11.4926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tan X. X., Tang C., Castoldi A. F., Manzo L., Costa L. G. Effects of inorganic and organic mercury on intracellular calcium levels in rat T lymphocytes. J Toxicol Environ Health. 1993 Feb;38(2):159–170. doi: 10.1080/15287399309531709. [DOI] [PubMed] [Google Scholar]
  22. Tipping P. G., Leong T. W., Holdsworth S. R. Tumor necrosis factor production by glomerular macrophages in anti-glomerular basement membrane glomerulonephritis in rabbits. Lab Invest. 1991 Sep;65(3):272–279. [PubMed] [Google Scholar]
  23. Williams A. F., Galfrè G., Milstein C. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977 Nov;12(3):663–673. doi: 10.1016/0092-8674(77)90266-5. [DOI] [PubMed] [Google Scholar]
  24. Yednock T. A., Cannon C., Fritz L. C., Sanchez-Madrid F., Steinman L., Karin N. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature. 1992 Mar 5;356(6364):63–66. doi: 10.1038/356063a0. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES