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Natural Resistance to Intracellular Infections: Natural Resistance–Associated Macrophage Protein 1 (Nramp1) Functions as a Ph-Dependent Manganese Transporter at the Phagosomal Membrane
Mutations at the natural resistance–associated macrophage protein 1 (Nramp1) locus cause susceptibility to infection with antigenically unrelated intracellular pathogens. Nramp1 codes for an integral membrane protein expressed in the lysosomal compartment of macrophages, and is recruited to the memb...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2000
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193348/ https://www.ncbi.nlm.nih.gov/pubmed/11067873 |
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author | Jabado, Nada Jankowski, Andrzej Dougaparsad, Samuel Picard, Virginie Grinstein, Sergio Gros, Philippe |
author_facet | Jabado, Nada Jankowski, Andrzej Dougaparsad, Samuel Picard, Virginie Grinstein, Sergio Gros, Philippe |
author_sort | Jabado, Nada |
collection | PubMed |
description | Mutations at the natural resistance–associated macrophage protein 1 (Nramp1) locus cause susceptibility to infection with antigenically unrelated intracellular pathogens. Nramp1 codes for an integral membrane protein expressed in the lysosomal compartment of macrophages, and is recruited to the membrane of phagosomes soon after the completion of phagocytosis. To define whether Nramp1 functions as a transporter at the phagosomal membrane, a divalent cation-sensitive fluorescent probe was designed and covalently attached to a porous particle. The resulting conjugate, zymosan–FF6, was ingested by macrophages and its fluorescence emission was recorded in situ after phagocytosis, using digital imaging. Quenching of the probe by Mn(2+) was used to monitor the flux of divalent cations across the phagosomal membrane in peritoneal macrophages obtained from Nramp1-expressing (+/+) and Nramp1-deficient (−/−) macrophages. Phagosomes from Nramp1(+/+) mice extrude Mn(2+) faster than their Nramp(−/−) counterparts. The difference in the rate of transport is eliminated when acidification of the phagosomal lumen is dissipated, suggesting that divalent metal transport through Nramp1 is H(+) dependent. These studies suggest that Nramp1 contributes to defense against infection by extrusion of divalent cations from the phagosomal space. Such cations are likely essential for microbial function and their removal from the phagosomal microenvironment impairs pathogenesis, resulting in enhanced bacteriostasis or bactericidal activity. |
format | Text |
id | pubmed-2193348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21933482008-04-16 Natural Resistance to Intracellular Infections: Natural Resistance–Associated Macrophage Protein 1 (Nramp1) Functions as a Ph-Dependent Manganese Transporter at the Phagosomal Membrane Jabado, Nada Jankowski, Andrzej Dougaparsad, Samuel Picard, Virginie Grinstein, Sergio Gros, Philippe J Exp Med Original Article Mutations at the natural resistance–associated macrophage protein 1 (Nramp1) locus cause susceptibility to infection with antigenically unrelated intracellular pathogens. Nramp1 codes for an integral membrane protein expressed in the lysosomal compartment of macrophages, and is recruited to the membrane of phagosomes soon after the completion of phagocytosis. To define whether Nramp1 functions as a transporter at the phagosomal membrane, a divalent cation-sensitive fluorescent probe was designed and covalently attached to a porous particle. The resulting conjugate, zymosan–FF6, was ingested by macrophages and its fluorescence emission was recorded in situ after phagocytosis, using digital imaging. Quenching of the probe by Mn(2+) was used to monitor the flux of divalent cations across the phagosomal membrane in peritoneal macrophages obtained from Nramp1-expressing (+/+) and Nramp1-deficient (−/−) macrophages. Phagosomes from Nramp1(+/+) mice extrude Mn(2+) faster than their Nramp(−/−) counterparts. The difference in the rate of transport is eliminated when acidification of the phagosomal lumen is dissipated, suggesting that divalent metal transport through Nramp1 is H(+) dependent. These studies suggest that Nramp1 contributes to defense against infection by extrusion of divalent cations from the phagosomal space. Such cations are likely essential for microbial function and their removal from the phagosomal microenvironment impairs pathogenesis, resulting in enhanced bacteriostasis or bactericidal activity. The Rockefeller University Press 2000-11-06 /pmc/articles/PMC2193348/ /pubmed/11067873 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Jabado, Nada Jankowski, Andrzej Dougaparsad, Samuel Picard, Virginie Grinstein, Sergio Gros, Philippe Natural Resistance to Intracellular Infections: Natural Resistance–Associated Macrophage Protein 1 (Nramp1) Functions as a Ph-Dependent Manganese Transporter at the Phagosomal Membrane |
title | Natural Resistance to Intracellular Infections: Natural Resistance–Associated Macrophage Protein 1 (Nramp1) Functions as a Ph-Dependent Manganese Transporter at the Phagosomal Membrane |
title_full | Natural Resistance to Intracellular Infections: Natural Resistance–Associated Macrophage Protein 1 (Nramp1) Functions as a Ph-Dependent Manganese Transporter at the Phagosomal Membrane |
title_fullStr | Natural Resistance to Intracellular Infections: Natural Resistance–Associated Macrophage Protein 1 (Nramp1) Functions as a Ph-Dependent Manganese Transporter at the Phagosomal Membrane |
title_full_unstemmed | Natural Resistance to Intracellular Infections: Natural Resistance–Associated Macrophage Protein 1 (Nramp1) Functions as a Ph-Dependent Manganese Transporter at the Phagosomal Membrane |
title_short | Natural Resistance to Intracellular Infections: Natural Resistance–Associated Macrophage Protein 1 (Nramp1) Functions as a Ph-Dependent Manganese Transporter at the Phagosomal Membrane |
title_sort | natural resistance to intracellular infections: natural resistance–associated macrophage protein 1 (nramp1) functions as a ph-dependent manganese transporter at the phagosomal membrane |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193348/ https://www.ncbi.nlm.nih.gov/pubmed/11067873 |
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