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Plasma iron controls neutrophil production and function

Low plasma iron (hypoferremia) induced by hepcidin is a conserved inflammatory response that protects against infections but inhibits erythropoiesis. How hypoferremia influences leukocytogenesis is unclear. Using proteomic data, we predicted that neutrophil production would be profoundly more iron-d...

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Autores principales: Frost, Joe N., Wideman, Sarah K., Preston, Alexandra E., Teh, Megan R., Ai, Zhichao, Wang, Lihui, Cross, Amy, White, Natasha, Yazicioglu, Yavuz, Bonadonna, Michael, Clarke, Alexander J., Armitage, Andrew E., Galy, Bruno, Udalova, Irina A., Drakesmith, Hal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534512/
https://www.ncbi.nlm.nih.gov/pubmed/36197985
http://dx.doi.org/10.1126/sciadv.abq5384
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author Frost, Joe N.
Wideman, Sarah K.
Preston, Alexandra E.
Teh, Megan R.
Ai, Zhichao
Wang, Lihui
Cross, Amy
White, Natasha
Yazicioglu, Yavuz
Bonadonna, Michael
Clarke, Alexander J.
Armitage, Andrew E.
Galy, Bruno
Udalova, Irina A.
Drakesmith, Hal
author_facet Frost, Joe N.
Wideman, Sarah K.
Preston, Alexandra E.
Teh, Megan R.
Ai, Zhichao
Wang, Lihui
Cross, Amy
White, Natasha
Yazicioglu, Yavuz
Bonadonna, Michael
Clarke, Alexander J.
Armitage, Andrew E.
Galy, Bruno
Udalova, Irina A.
Drakesmith, Hal
author_sort Frost, Joe N.
collection PubMed
description Low plasma iron (hypoferremia) induced by hepcidin is a conserved inflammatory response that protects against infections but inhibits erythropoiesis. How hypoferremia influences leukocytogenesis is unclear. Using proteomic data, we predicted that neutrophil production would be profoundly more iron-demanding than generation of other white blood cell types. Accordingly in mice, hepcidin-mediated hypoferremia substantially reduced numbers of granulocytes but not monocytes, lymphocytes, or dendritic cells. Neutrophil rebound after anti-Gr-1–induced neutropenia was blunted during hypoferremia but was rescued by supplemental iron. Similarly, hypoferremia markedly inhibited pharmacologically stimulated granulopoiesis mediated by granulocyte colony-stimulating factor and inflammation-induced accumulation of neutrophils in the spleen and peritoneal cavity. Furthermore, hypoferremia specifically altered neutrophil effector functions, suppressing antibacterial mechanisms but enhancing mitochondrial reactive oxygen species–dependent NETosis associated with chronic inflammation. Notably, antagonizing endogenous hepcidin during acute inflammation enhanced production of neutrophils. We propose plasma iron modulates the profile of innate immunity by controlling monocyte-to-neutrophil ratio and neutrophil activity in a therapeutically targetable system.
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spelling pubmed-95345122022-10-24 Plasma iron controls neutrophil production and function Frost, Joe N. Wideman, Sarah K. Preston, Alexandra E. Teh, Megan R. Ai, Zhichao Wang, Lihui Cross, Amy White, Natasha Yazicioglu, Yavuz Bonadonna, Michael Clarke, Alexander J. Armitage, Andrew E. Galy, Bruno Udalova, Irina A. Drakesmith, Hal Sci Adv Biomedicine and Life Sciences Low plasma iron (hypoferremia) induced by hepcidin is a conserved inflammatory response that protects against infections but inhibits erythropoiesis. How hypoferremia influences leukocytogenesis is unclear. Using proteomic data, we predicted that neutrophil production would be profoundly more iron-demanding than generation of other white blood cell types. Accordingly in mice, hepcidin-mediated hypoferremia substantially reduced numbers of granulocytes but not monocytes, lymphocytes, or dendritic cells. Neutrophil rebound after anti-Gr-1–induced neutropenia was blunted during hypoferremia but was rescued by supplemental iron. Similarly, hypoferremia markedly inhibited pharmacologically stimulated granulopoiesis mediated by granulocyte colony-stimulating factor and inflammation-induced accumulation of neutrophils in the spleen and peritoneal cavity. Furthermore, hypoferremia specifically altered neutrophil effector functions, suppressing antibacterial mechanisms but enhancing mitochondrial reactive oxygen species–dependent NETosis associated with chronic inflammation. Notably, antagonizing endogenous hepcidin during acute inflammation enhanced production of neutrophils. We propose plasma iron modulates the profile of innate immunity by controlling monocyte-to-neutrophil ratio and neutrophil activity in a therapeutically targetable system. American Association for the Advancement of Science 2022-10-05 /pmc/articles/PMC9534512/ /pubmed/36197985 http://dx.doi.org/10.1126/sciadv.abq5384 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Frost, Joe N.
Wideman, Sarah K.
Preston, Alexandra E.
Teh, Megan R.
Ai, Zhichao
Wang, Lihui
Cross, Amy
White, Natasha
Yazicioglu, Yavuz
Bonadonna, Michael
Clarke, Alexander J.
Armitage, Andrew E.
Galy, Bruno
Udalova, Irina A.
Drakesmith, Hal
Plasma iron controls neutrophil production and function
title Plasma iron controls neutrophil production and function
title_full Plasma iron controls neutrophil production and function
title_fullStr Plasma iron controls neutrophil production and function
title_full_unstemmed Plasma iron controls neutrophil production and function
title_short Plasma iron controls neutrophil production and function
title_sort plasma iron controls neutrophil production and function
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534512/
https://www.ncbi.nlm.nih.gov/pubmed/36197985
http://dx.doi.org/10.1126/sciadv.abq5384
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