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Infection and Immunity, March 1999, p. 1386-1392, Vol. 67, No. 3
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-
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Copyright © 1999, American Society for Microbiology. All rights reserved.
Role of Iron in Nramp1-Mediated
Inhibition of Mycobacterial Growth
)-activated macrophages with iron, we found that iron abrogated the growth inhibitory effect of IFN-
-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.
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