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Cited by 79Iron Metabolism and DisordersMycobacterium research and diagnosisTuberculosis Research and Epidemiology

Iron transport into Mycobacterium avium-containing phagosomes from an Nramp1Gly169-transfected RAW264.7 macrophage cell line

Kuhn, Donald E, Lafuse, William P, Zwilling, Bruce S·2001·Journal of Leukocyte Biology
DOI 10.1189/jlb.69.1.43
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Abstract

Nramp1 is an important determinant of innate resistance of macrophages to the growth of intracellular microorganisms. We previously showed that Nramp1 functions to transport iron from the cytoplasm into phagosomes of Mycobacterium avium-infected macrophages. The purpose of this investigation was to further characterize the factors that regulate Nramp1-mediated iron transport into phagosomes. Treatment of Nramp1Gly169 macrophages with the lysomotrophic agents chloroquine or ammonium chloride reduced the import of iron significantly. We found that macrophage-activating cytokines, including TNF-α, IFN-γ, IL-1α, and GM-CSF, when added prior to M. avium, increased the transport of iron into the phagosome. This increase in iron transport was not a result of an increased amount of Nramp1 protein in the phagosome nor to new protein synthesis. Treatment of Nramp1Gly169-transfected macrophages with inhibitors of protein kinase C (PKC) diminished the import of iron into the phagosomes. Iron import was inhibited by an anti-Nramp1 antibody against the putative fourth outer-loop region of Nramp1 but not by an anti-Nramp1 antibody against the carboxy terminus. The significance of these results on the orientation of Nramp1 in the phagosome membrane and on the transport of iron is discussed.

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Crossref · 10.1189/jlb.69.1.43

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  • NRAMP1 is a divalent metal ion transporter that pumps iron out of the phagolysosome into the macrophage cytoplasm to limit iron-access to intracellular pathogens.

    “This protein is a divalent metal ion transporter that pumps iron out of the phagolysosome into the macrophage cytoplasm to limit iron-access to intracellular pathogens (Kuhn et al., 2001).”

    From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Kuhn et al., 2001

  • Some data suggest that Nramp1 pumps iron into the phagolysosome where it may boost ROS generation.

    “However, some data suggest that Nramp1 in fact pumps iron into the phagolysosome where it may boost ROS generation [121, 122].”

    From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [122]

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Authors
Kuhn, D. E., Lafuse, W. P., & Zwilling, B. S.
Affiliations
The Ohio State University (US)
Corresponding author
Zwilling, Bruce S
ORCID
Lafuse, William P
Venue
Journal of Leukocyte Biology
Publisher
Oxford University Press (OUP)
Published
2001-01-01
Volume
69
Issue
1
Pages
43-49
ISSN
  • 0741-5400 (ISSN-L)
  • 1938-3673
DOI
10.1189/jlb.69.1.43
OpenAlex
W2410274080
Cited by
79
References
27
Citations by year
2026: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2014: 5 · 2013: 3 · 2012: 3
FWCI
3.89
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • Journal of Leukocyte Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
USPHS (HL59795, DK57667, AI42901, MH54966)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Keywords
NRAMP1, iron transport, phagosome, Mycobacterium avium, macrophages, RAW 264.7 macrophages, lysosomal iron, chloroquine, ammonium chloride, TNF-α, interferon-gamma, IL-1α, GM-CSF, protein kinase C, antibody inhibition
MeSH terms
Natural Resistance-associated Macrophage Protein 1, Animals, Carrier Proteins, Iron, Macrophages, Membrane Proteins, Mycobacterium avium, Phagosomes, Gene Expression Regulation, Bacterial, Ion Transport, Cation Transport Proteins, Mice

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