Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 Aug;63(8):2983–2988. doi: 10.1128/iai.63.8.2983-2988.1995

Cytokine-mediated activation of macrophages from Mycobacterium bovis BCG-resistant and -susceptible mice: differential effects of corticosterone on antimycobacterial activity and expression of the Bcg gene (Candidate Nramp).

D H Brown 1, W LaFuse 1, B S Zwilling 1
PMCID: PMC173405  PMID: 7622220

Abstract

Previous work in our laboratory has shown that corticosterone increases the susceptibility of macrophages from Bcgs mice to the growth of Mycobacterium avium. The innate antimycobacterial activity of macrophages from Bcgr mice was not affected by corticosterone. In contrast to the differential effect of corticosterone on the antimycobacterial activity of the macrophages, corticosterone suppressed the production of tumor necrosis factor alpha and nitric oxide by macrophages from both Bcgr and Bcgs mice. The purpose of this investigation was to compare the effects of corticosterone on the antimycobacterial activity of macrophages from Bcgr and Bcgs mice that have been activated in vitro with recombinant gamma interferon or granulocyte-macrophage colony-stimulating factor. We found that macrophages from both strains of congenic mice responded equally to the activation stimuli. The capacity of the activated macrophages from Bcgs mice to suppress the growth of M. avium was inhibited by the addition of corticosterone to the cultures. The addition of NG-monomethyl-L-arginine to the cultures did not affect the capacity of resident splenic macrophages from Bcgr mice to limit the growth of M. avium. However, NG-monomethyl-L-arginine reduced the capacity of gamma interferon-activated, but not granulocyte-macrophage colony-stimulating factor-activated, macrophages to limit the growth of M. avium by macrophages from both Bcgr and Bcgs mice. The addition of corticosterone suppressed Nramp expression by macrophages from Bcgs mice. Nramp expression by macrophages from Bcgr mice was not affected by corticosterone.

Full Text

The Full Text of this article is available as a PDF (435.9 KB).

Selected References

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

  1. Appelberg R., Orme I. M. Effector mechanisms involved in cytokine-mediated bacteriostasis of Mycobacterium avium infections in murine macrophages. Immunology. 1993 Nov;80(3):352–359. [PMC free article] [PubMed] [Google Scholar]
  2. Barrera L. F., Kramnik I., Skamene E., Radzioch D. Nitrite production by macrophages derived from BCG-resistant and -susceptible congenic mouse strains in response to IFN-gamma and infection with BCG. Immunology. 1994 Jul;82(3):457–464. [PMC free article] [PubMed] [Google Scholar]
  3. Bermudez L. E., Young L. S. Recombinant granulocyte-macrophage colony-stimulating factor activates human macrophages to inhibit growth or kill Mycobacterium avium complex. J Leukoc Biol. 1990 Jul;48(1):67–73. doi: 10.1002/jlb.48.1.67. [DOI] [PubMed] [Google Scholar]
  4. Brown D. H., Sheridan J., Pearl D., Zwilling B. S. Regulation of mycobacterial growth by the hypothalamus-pituitary-adrenal axis: differential responses of Mycobacterium bovis BCG-resistant and -susceptible mice. Infect Immun. 1993 Nov;61(11):4793–4800. doi: 10.1128/iai.61.11.4793-4800.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown D. H., Zwilling B. S. Activation of the hypothalamic-pituitary-adrenal axis differentially affects the anti-mycobacterial activity of macrophages from BCG-resistant and susceptible mice. J Neuroimmunol. 1994 Sep;53(2):181–187. doi: 10.1016/0165-5728(94)90028-0. [DOI] [PubMed] [Google Scholar]
  6. Buisman A., van Dissel J. T., Langermans J. A., van Furth R. Granulocyte-macrophage colony-stimulating factor is not involved in production of reactive nitrogen intermediates by or toxoplasmastatic activity of gamma interferon-activated murine macrophages. Infect Immun. 1994 Mar;62(3):1121–1124. doi: 10.1128/iai.62.3.1121-1124.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chan J., Xing Y., Magliozzo R. S., Bloom B. R. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J Exp Med. 1992 Apr 1;175(4):1111–1122. doi: 10.1084/jem.175.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Denis M. Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates. J Leukoc Biol. 1991 Apr;49(4):380–387. doi: 10.1002/jlb.49.4.380. [DOI] [PubMed] [Google Scholar]
  9. Evans R., Kamdar S. J. Stability of RNA isolated from macrophages depends on the removal of an RNA-degrading activity early in the extraction procedure. Biotechniques. 1990 Apr;8(4):357–360. [PubMed] [Google Scholar]
  10. Flesch I. E., Kaufmann S. H. Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates. Infect Immun. 1991 Sep;59(9):3213–3218. doi: 10.1128/iai.59.9.3213-3218.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Formica S., Roach T. I., Blackwell J. M. Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release. Immunology. 1994 May;82(1):42–50. [PMC free article] [PubMed] [Google Scholar]
  12. Gazzinelli R. T., Eltoum I., Wynn T. A., Sher A. Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol. 1993 Oct 1;151(7):3672–3681. [PubMed] [Google Scholar]
  13. Gebran S. J., Yamamoto Y., Newton C., Klein T. W., Friedman H. Inhibition of Legionella pneumophila growth by gamma interferon in permissive A/J mouse macrophages: role of reactive oxygen species, nitric oxide, tryptophan, and iron(III). Infect Immun. 1994 Aug;62(8):3197–3205. doi: 10.1128/iai.62.8.3197-3205.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Green L. C., Wagner D. A., Glogowski J., Skipper P. L., Wishnok J. S., Tannenbaum S. R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982 Oct;126(1):131–138. doi: 10.1016/0003-2697(82)90118-x. [DOI] [PubMed] [Google Scholar]
  15. Green S. J., Nacy C. A., Schreiber R. D., Granger D. L., Crawford R. M., Meltzer M. S., Fortier A. H. Neutralization of gamma interferon and tumor necrosis factor alpha blocks in vivo synthesis of nitrogen oxides from L-arginine and protection against Francisella tularensis infection in Mycobacterium bovis BCG-treated mice. Infect Immun. 1993 Feb;61(2):689–698. doi: 10.1128/iai.61.2.689-698.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Heidenreich S., Gong J. H., Schmidt A., Nain M., Gemsa D. Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2. J Immunol. 1989 Aug 15;143(4):1198–1205. [PubMed] [Google Scholar]
  17. Jacobsson A., Stadler U., Glotzer M. A., Kozak L. P. Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression. J Biol Chem. 1985 Dec 25;260(30):16250–16254. [PubMed] [Google Scholar]
  18. Morrissey P. J., Bressler L., Charrier K., Alpert A. Response of resident murine peritoneal macrophages to in vivo administration of granulocyte-macrophage colony-stimulating factor. J Immunol. 1988 Mar 15;140(6):1910–1915. [PubMed] [Google Scholar]
  19. Morrissey P. J., Charrier K. GM-CSF administration augments the survival of ity-resistant A/J mice, but not ity-susceptible C57BL/6 mice, to a lethal challenge with Salmonella typhimurium. J Immunol. 1990 Jan 15;144(2):557–561. [PubMed] [Google Scholar]
  20. Nibbering P. H., Yoshida S. I., van den Barselaar M. T., van Furth R. Bacteriostatic activity of BCG/PPD-activated macrophages against Mycobacterium fortuitum does not involve reactive nitrogen or oxygen intermediates. Scand J Immunol. 1994 Aug;40(2):187–194. doi: 10.1111/j.1365-3083.1994.tb03449.x. [DOI] [PubMed] [Google Scholar]
  21. Polsinelli T., Meltzer M. S., Fortier A. H. Nitric oxide-independent killing of Francisella tularensis by IFN-gamma-stimulated murine alveolar macrophages. J Immunol. 1994 Aug 1;153(3):1238–1245. [PubMed] [Google Scholar]
  22. Potter M., O'Brien A. D., Skamene E., Gros P., Forget A., Kongshavn P. A., Wax J. S. A BALB/c congenic strain of mice that carries a genetic locus (Ityr) controlling resistance to intracellular parasites. Infect Immun. 1983 Jun;40(3):1234–1235. doi: 10.1128/iai.40.3.1234-1235.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Roach T. I., Chatterjee D., Blackwell J. M. Induction of early-response genes KC and JE by mycobacterial lipoarabinomannans: regulation of KC expression in murine macrophages by Lsh/Ity/Bcg (candidate Nramp). Infect Immun. 1994 Apr;62(4):1176–1184. doi: 10.1128/iai.62.4.1176-1184.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Roach T. I., Kiderlen A. F., Blackwell J. M. Role of inorganic nitrogen oxides and tumor necrosis factor alpha in killing Leishmania donovani amastigotes in gamma interferon-lipopolysaccharide-activated macrophages from Lshs and Lshr congenic mouse strains. Infect Immun. 1991 Nov;59(11):3935–3944. doi: 10.1128/iai.59.11.3935-3944.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schurr E., Skamene E., Forget A., Gros P. Linkage analysis of the Bcg gene on mouse chromosome 1. Identification of a tightly linked marker. J Immunol. 1989 Jun 15;142(12):4507–4513. [PubMed] [Google Scholar]
  26. Stenger S., Thüring H., Röllinghoff M., Bogdan C. Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major. J Exp Med. 1994 Sep 1;180(3):783–793. doi: 10.1084/jem.180.3.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Suzuki K., Lee W. J., Hashimoto T., Tanaka E., Murayama T., Amitani R., Yamamoto K., Kuze F. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumour necrosis factor-alpha (TNF-alpha) activate human alveolar macrophages to inhibit growth of Mycobacterium avium complex. Clin Exp Immunol. 1994 Oct;98(1):169–173. doi: 10.1111/j.1365-2249.1994.tb06625.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vidal S. M., Malo D., Vogan K., Skamene E., Gros P. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell. 1993 May 7;73(3):469–485. doi: 10.1016/0092-8674(93)90135-d. [DOI] [PubMed] [Google Scholar]
  29. Wang M., Friedman H., Djeu J. Y. Enhancement of human monocyte function against Candida albicans by the colony-stimulating factors (CSF): IL-3, granulocyte-macrophage-CSF, and macrophage-CSF. J Immunol. 1989 Jul 15;143(2):671–677. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES