This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zwilling, B. S.
Right arrow Articles by Lafuse, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zwilling, B. S.
Right arrow Articles by Lafuse, W.

 Previous Article  |  Next Article 

Infection and Immunity, March 1999, p. 1386-1392, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of Iron in Nramp1-Mediated Inhibition of Mycobacterial Growth

Bruce S. Zwilling,1,2,* Donald E. Kuhn,1 Lisa Wikoff,1 David Brown,1 and William Lafuse2

Departments of Microbiology1 and Medical Microbiology and Immunology,2 The Ohio State University, Columbus, Ohio 43210

Received 8 October 1998/Accepted 1 December 1998

Innate resistance to mycobacterial growth is mediated by a gene, Nramp1. We have previously reported that Nramp1 mRNA from macrophages of Mycobacterium bovis BCG-resistant (Bcgr) mice is more stable than Nramp1 mRNA from macrophages of BCG-susceptible (Bcgs) mice. Based on these observations and on reports that show that the closely related Nramp2 gene is a metal ion transporter, we evaluated the effect of iron on the growth of Mycobacterium avium within macrophages as well as on the stability of Nramp1 mRNA. The addition of iron to macrophages from Bcgs mice resulted in a stimulation of mycobacterial growth. In contrast, iron increased the capacity of macrophages from Bcgr mice to control the growth of M. avium. When we treated recombinant gamma interferon (IFN-gamma )-activated macrophages with iron, we found that iron abrogated the growth inhibitory effect of IFN-gamma -activated macrophages from Bcgs mice but that it did not affect the capacity of macrophages from Bcgr mice to control microbial growth. A more detailed examination of the effect of iron on microbial growth showed that the addition of small quantities of iron to resident macrophages from Bcgr mice stimulated antimicrobial activity within a very narrow dose range. The effect of iron on the growth inhibitory activity of macrophages from Bcgr mice was abrogated by the addition of catalase or mannitol to the culture medium. These results are consistent with an Fe(II)-mediated stimulation of the Fenton/Haber-Weiss reaction and hydroxyl radical-mediated inhibition of mycobacterial growth.

* Corresponding author. Mailing address: Department of Microbiology, College of Biological Sciences, 484 West 12th Ave., Columbus, Ohio 43210. Phone: (614) 292-3310. Fax: (614) 292-8120. E-mail: zwilling.1{at}osu.edu.

Infection and Immunity, March 1999, p. 1386-1392, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Shi, Z., Sun, J., Guo, H., Tu, C. (2009). Genomic expression profiling of peripheral blood leukocytes of pigs infected with highly virulent classical swine fever virus strain Shimen. J. Gen. Virol. 90: 1670-1680 [Abstract] [Full Text]  
  • Van Zandt, K. E., Sow, F. B., Florence, W. C., Zwilling, B. S., Satoskar, A. R., Schlesinger, L. S., Lafuse, W. P. (2008). The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome. J. Leukoc. Biol. 84: 689-700 [Abstract] [Full Text]  
  • Roupie, V., Rosseels, V., Piersoel, V., Zinniel, D. K., Barletta, R. G., Huygen, K. (2008). Genetic Resistance of Mice to Mycobacterium paratuberculosis Is Influenced by Slc11a1 at the Early but Not at the Late Stage of Infection. Infect. Immun. 76: 2099-2105 [Abstract] [Full Text]  
  • Gomez, M. A., Li, S., Tremblay, M. L., Olivier, M. (2007). NRAMP-1 Expression Modulates Protein-tyrosine Phosphatase Activity in Macrophages: IMPACT ON HOST CELL SIGNALING AND FUNCTIONS. J. Biol. Chem. 282: 36190-36198 [Abstract] [Full Text]  
  • Techau, M. E., Valdez-Taubas, J., Popoff, J.-F., Francis, R., Seaman, M., Blackwell, J. M. (2007). Evolution of Differences in Transport Function in Slc11a Family Members. J. Biol. Chem. 282: 35646-35656 [Abstract] [Full Text]  
  • Olakanmi, O., Schlesinger, L. S., Britigan, B. E. (2007). Hereditary hemochromatosis results in decreased iron acquisition and growth by Mycobacterium tuberculosis within human macrophages. J. Leukoc. Biol. 81: 195-204 [Abstract] [Full Text]  
  • Huynh, C., Sacks, D. L., Andrews, N. W. (2006). A Leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes. JEM 203: 2363-2375 [Abstract] [Full Text]  
  • Knowles, H. J., Mole, D. R., Ratcliffe, P. J., Harris, A. L. (2006). Normoxic Stabilization of Hypoxia-Inducible Factor-1{alpha} by Modulation of the Labile Iron Pool in Differentiating U937 Macrophages: Effect of Natural Resistance-Associated Macrophage Protein 1.. Cancer Res. 66: 2600-2607 [Abstract] [Full Text]  
  • Olakanmi, O., Schlesinger, L. S., Ahmed, A., Britigan, B. E. (2004). The Nature of Extracellular Iron Influences Iron Acquisition by Mycobacterium tuberculosis Residing within Human Macrophages. Infect. Immun. 72: 2022-2028 [Abstract] [Full Text]  
  • Ashrafian, H. (2003). Hepcidin: the Missing Link between Hemochromatosis and Infections. Infect. Immun. 71: 6693-6700 [Full Text]  
  • Forbes, J. R., Gros, P. (2003). Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood 102: 1884-1892 [Abstract] [Full Text]  
  • Fritsche, G., Dlaska, M., Barton, H., Theurl, I., Garimorth, K., Weiss, G. (2003). Nramp1 Functionality Increases Inducible Nitric Oxide Synthase Transcription Via Stimulation of IFN Regulatory Factor 1 Expression. J. Immunol. 171: 1994-1998 [Abstract] [Full Text]  
  • Smit, J. J., Van Loveren, H., Hoekstra, M. O., Karimi, K., Folkerts, G., Nijkamp, F. P. (2003). The Slc11a1 (Nramp1) Gene Controls Efficacy of Mycobacterial Treatment of Allergic Asthma. J. Immunol. 171: 754-760 [Abstract] [Full Text]  
  • Olakanmi, O., Schlesinger, L. S., Ahmed, A., Britigan, B. E. (2002). Intraphagosomal Mycobacterium tuberculosis Acquires Iron from Both Extracellular Transferrin and Intracellular Iron Pools. IMPACT OF INTERFERON-gamma AND HEMOCHROMATOSIS. J. Biol. Chem. 277: 49727-49734 [Abstract] [Full Text]  
  • Wyllie, S., Seu, P., Gao, F. Q., Gros, P., Goss, J. A. (2002). Disruption of the Nramp1 (also known as Slc11a1) gene in Kupffer cells attenuates early-phase, warm ischemia-reperfusion injury in the mouse liver. J. Leukoc. Biol. 72: 885-897 [Abstract] [Full Text]  
  • Gomes, M. S., Appelberg, R. (2002). NRAMP1- or cytokine-induced bacteriostasis of Mycobacterium avium by mouse macrophages is independent of the respiratory burst. Microbiology 148: 3155-3160 [Abstract] [Full Text]  
  • van Crevel, R., Ottenhoff, T. H. M., van der Meer, J. W. M. (2002). Innate Immunity to Mycobacterium tuberculosis. Clin. Microbiol. Rev. 15: 294-309 [Abstract] [Full Text]  
  • Collins, H. L., Kaufmann, S. H. E., Schaible, U. E. (2002). Iron Chelation Via Deferoxamine Exacerbates Experimental Salmonellosis Via Inhibition of the Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Dependent Respiratory Burst. J. Immunol. 168: 3458-3463 [Abstract] [Full Text]  
  • Wardrop, S. L., Wells, C., Ravasi, T., Hume, D. A., Richardson, D. R. (2002). Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism. J. Leukoc. Biol. 71: 99-106 [Abstract] [Full Text]  
  • Zhong, W., Lafuse, W. P., Zwilling, B. S. (2001). Infection with Mycobacterium avium Differentially Regulates the Expression of Iron Transport Protein mRNA in Murine Peritoneal Macrophages. Infect. Immun. 69: 6618-6624 [Abstract] [Full Text]  
  • Fairbairn, I. P., Stober, C. B., Kumararatne, D. S., Lammas, D. A. (2001). ATP-Mediated Killing of Intracellular Mycobacteria by Macrophages Is a P2X7-Dependent Process Inducing Bacterial Death by Phagosome-Lysosome Fusion. J. Immunol. 167: 3300-3307 [Abstract] [Full Text]  
  • Jabado, N., Jankowski, A., Dougaparsad, S., Picard, V., Grinstein, S., Gros, P. (2000). Natural resistance to intracellular infections: natural resistance-associated macrophage protein 1 (NRAMP1) functions as a pH-dependent manganese transporter at the phagosomal membrane. JEM 192: 1237-1248 [Abstract] [Full Text]  
  • Olakanmi, O., Britigan, B. E., Schlesinger, L. S. (2000). Gallium Disrupts Iron Metabolism of Mycobacteria Residing within Human Macrophages. Infect. Immun. 68: 5619-5627 [Abstract] [Full Text]  
  • Wright, A. D., Chapes, S. K. (1999). LPS sensitivity in recombinant mice lacking functional alleles at MHCII, Lps and Nramp1 genes. Innate Immunity 5: 297-305 [Abstract]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»