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Pulmonary Iron Homeostasis in Hepcidin Knockout Mice

Pulmonary iron excess is deleterious and contributes to a range of chronic and acute inflammatory diseases. Optimal lung iron concentration is maintained through dynamic regulation of iron transport and storage proteins. The iron-regulatory hormone hepcidin is also expressed in the lung. In order to...

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Autores principales: Deschemin, Jean-Christophe, Mathieu, Jacques R. R., Zumerle, Sara, Peyssonnaux, Carole, Vaulont, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650979/
https://www.ncbi.nlm.nih.gov/pubmed/29089902
http://dx.doi.org/10.3389/fphys.2017.00804
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author Deschemin, Jean-Christophe
Mathieu, Jacques R. R.
Zumerle, Sara
Peyssonnaux, Carole
Vaulont, Sophie
author_facet Deschemin, Jean-Christophe
Mathieu, Jacques R. R.
Zumerle, Sara
Peyssonnaux, Carole
Vaulont, Sophie
author_sort Deschemin, Jean-Christophe
collection PubMed
description Pulmonary iron excess is deleterious and contributes to a range of chronic and acute inflammatory diseases. Optimal lung iron concentration is maintained through dynamic regulation of iron transport and storage proteins. The iron-regulatory hormone hepcidin is also expressed in the lung. In order to better understand the interactions between iron-associated molecules and the hepcidin-ferroportin axis in lung iron balance, we examined lung physiology and inflammatory responses in two murine models of systemic iron-loading, either hepcidin knock-out (Hepc KO) or liver-specific hepcidin KO mice (Hepc KOliv), which do (Hepc KOliv) or do not (Hepc KO) express lung hepcidin. We have found that increased plasma iron in Hepc KO mice is associated with increased pulmonary iron levels, consistent with increased cellular iron uptake by pulmonary epithelial cells, together with an increase at the apical membrane of the cells of the iron exporter ferroportin, consistent with increased iron export in the alveoli. Subsequently, alveolar macrophages (AM) accumulate iron in a non-toxic form and this is associated with elevated production of ferritin. The accumulation of iron in the lung macrophages of hepcidin KO mice contrasts with splenic and hepatic macrophages which contain low iron levels as we have previously reported. Hepc KOliv mice with liver-specific hepcidin deficiency demonstrated same pulmonary iron overload profile as the Hepc KO mice, suggesting that pulmonary hepcidin is not critical in maintaining local iron homeostasis. In addition, the high iron load in the lung of Hepc KO mice does not appear to enhance acute lung inflammation or injury. Lastly, we have shown that intraperitoneal LPS injection is not associated with pulmonary hepcidin induction, despite high levels of inflammatory cytokines. However, intranasal LPS injection stimulates a hepcidin response, likely derived from AM, and alters pulmonary iron content in Hepc KO mice.
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spelling pubmed-56509792017-10-31 Pulmonary Iron Homeostasis in Hepcidin Knockout Mice Deschemin, Jean-Christophe Mathieu, Jacques R. R. Zumerle, Sara Peyssonnaux, Carole Vaulont, Sophie Front Physiol Physiology Pulmonary iron excess is deleterious and contributes to a range of chronic and acute inflammatory diseases. Optimal lung iron concentration is maintained through dynamic regulation of iron transport and storage proteins. The iron-regulatory hormone hepcidin is also expressed in the lung. In order to better understand the interactions between iron-associated molecules and the hepcidin-ferroportin axis in lung iron balance, we examined lung physiology and inflammatory responses in two murine models of systemic iron-loading, either hepcidin knock-out (Hepc KO) or liver-specific hepcidin KO mice (Hepc KOliv), which do (Hepc KOliv) or do not (Hepc KO) express lung hepcidin. We have found that increased plasma iron in Hepc KO mice is associated with increased pulmonary iron levels, consistent with increased cellular iron uptake by pulmonary epithelial cells, together with an increase at the apical membrane of the cells of the iron exporter ferroportin, consistent with increased iron export in the alveoli. Subsequently, alveolar macrophages (AM) accumulate iron in a non-toxic form and this is associated with elevated production of ferritin. The accumulation of iron in the lung macrophages of hepcidin KO mice contrasts with splenic and hepatic macrophages which contain low iron levels as we have previously reported. Hepc KOliv mice with liver-specific hepcidin deficiency demonstrated same pulmonary iron overload profile as the Hepc KO mice, suggesting that pulmonary hepcidin is not critical in maintaining local iron homeostasis. In addition, the high iron load in the lung of Hepc KO mice does not appear to enhance acute lung inflammation or injury. Lastly, we have shown that intraperitoneal LPS injection is not associated with pulmonary hepcidin induction, despite high levels of inflammatory cytokines. However, intranasal LPS injection stimulates a hepcidin response, likely derived from AM, and alters pulmonary iron content in Hepc KO mice. Frontiers Media S.A. 2017-10-17 /pmc/articles/PMC5650979/ /pubmed/29089902 http://dx.doi.org/10.3389/fphys.2017.00804 Text en Copyright © 2017 Deschemin, Mathieu, Zumerle, Peyssonnaux and Vaulont. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Deschemin, Jean-Christophe
Mathieu, Jacques R. R.
Zumerle, Sara
Peyssonnaux, Carole
Vaulont, Sophie
Pulmonary Iron Homeostasis in Hepcidin Knockout Mice
title Pulmonary Iron Homeostasis in Hepcidin Knockout Mice
title_full Pulmonary Iron Homeostasis in Hepcidin Knockout Mice
title_fullStr Pulmonary Iron Homeostasis in Hepcidin Knockout Mice
title_full_unstemmed Pulmonary Iron Homeostasis in Hepcidin Knockout Mice
title_short Pulmonary Iron Homeostasis in Hepcidin Knockout Mice
title_sort pulmonary iron homeostasis in hepcidin knockout mice
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650979/
https://www.ncbi.nlm.nih.gov/pubmed/29089902
http://dx.doi.org/10.3389/fphys.2017.00804
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