Role of iron in Nramp1-mediated inhibition of mycobacterial growth.
Role of iron in Nramp1-mediated inhibition of mycobacterial growth.
复制标题
铁在 Nramp1 介导的分枝杆菌生长抑制中的作用。
DOI：
10.1128/iai.67.3.1386-1392.1999
复制
发表时间：
1999
影响因子：
3.1
通讯作者：
Lafuse,W
中科院分区：
文献类型：
--
作者：
Zwilling,BS;Kuhn,DE;Wikoff,L;Brown,D;Lafuse,W
Innate resistance to mycobacterial growth is mediated by a gene,Nramp1. We have previously reported thatNramp1mRNA from macrophages ofMycobacterium bovisBCG-resistant (Bcgr) mice is more stable thanNramp1mRNA from macrophages of BCG-susceptible (Bcgs) mice. Based on these observations and on reports that show that the closely relatedNramp2gene is a metal ion transporter, we evaluated the effect of iron on the growth ofMycobacterium aviumwithin macrophages as well as on the stability ofNramp1mRNA. The addition of iron to macrophages fromBcgsmice resulted in a stimulation of mycobacterial growth. In contrast, iron increased the capacity of macrophages fromBcgrmice to control the growth ofM. avium. When we treated recombinant gamma interferon (IFN-γ)-activated macrophages with iron, we found that iron abrogated the growth inhibitory effect of IFN-γ-activated macrophages fromBcgsmice but that it did not affect the capacity of macrophages fromBcgrmice 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 fromBcgrmice stimulated antimicrobial activity within a very narrow dose range. The effect of iron on the growth inhibitory activity of macrophages fromBcgrmice 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.
