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Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils
Neutrophils are cells at the frontline of innate immunity that can quickly activate effector functions to eliminate pathogens upon stimulation. However, little is known about the metabolic adaptations that power these functions. Here we show rapid metabolic alterations in neutrophils upon activation...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964420/ https://www.ncbi.nlm.nih.gov/pubmed/35347316 http://dx.doi.org/10.1038/s42255-022-00550-8 |
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author | Britt, Emily C. Lika, Jorgo Giese, Morgan A. Schoen, Taylor J. Seim, Gretchen L. Huang, Zhengping Lee, Pui Y. Huttenlocher, Anna Fan, Jing |
author_facet | Britt, Emily C. Lika, Jorgo Giese, Morgan A. Schoen, Taylor J. Seim, Gretchen L. Huang, Zhengping Lee, Pui Y. Huttenlocher, Anna Fan, Jing |
author_sort | Britt, Emily C. |
collection | PubMed |
description | Neutrophils are cells at the frontline of innate immunity that can quickly activate effector functions to eliminate pathogens upon stimulation. However, little is known about the metabolic adaptations that power these functions. Here we show rapid metabolic alterations in neutrophils upon activation, particularly drastic reconfiguration around the pentose phosphate pathway, which is specifically and quantitatively coupled to an oxidative burst. During this oxidative burst, neutrophils switch from glycolysis-dominant metabolism to a unique metabolic mode termed ‘pentose cycle’, where all glucose-6-phosphate is diverted into oxidative pentose phosphate pathway and net flux through upper glycolysis is reversed to allow substantial recycling of pentose phosphates. This reconfiguration maximizes NADPH yield to fuel superoxide production via NADPH oxidase. Disruptions of pentose cycle greatly suppress oxidative burst, the release of neutrophil extracellular traps and pathogen killing by neutrophils. Together, these results demonstrate the remarkable metabolic flexibility of neutrophils, which is essential for their functions as the first responders in innate immunity. |
format | Online Article Text |
id | pubmed-8964420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89644202022-04-07 Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils Britt, Emily C. Lika, Jorgo Giese, Morgan A. Schoen, Taylor J. Seim, Gretchen L. Huang, Zhengping Lee, Pui Y. Huttenlocher, Anna Fan, Jing Nat Metab Article Neutrophils are cells at the frontline of innate immunity that can quickly activate effector functions to eliminate pathogens upon stimulation. However, little is known about the metabolic adaptations that power these functions. Here we show rapid metabolic alterations in neutrophils upon activation, particularly drastic reconfiguration around the pentose phosphate pathway, which is specifically and quantitatively coupled to an oxidative burst. During this oxidative burst, neutrophils switch from glycolysis-dominant metabolism to a unique metabolic mode termed ‘pentose cycle’, where all glucose-6-phosphate is diverted into oxidative pentose phosphate pathway and net flux through upper glycolysis is reversed to allow substantial recycling of pentose phosphates. This reconfiguration maximizes NADPH yield to fuel superoxide production via NADPH oxidase. Disruptions of pentose cycle greatly suppress oxidative burst, the release of neutrophil extracellular traps and pathogen killing by neutrophils. Together, these results demonstrate the remarkable metabolic flexibility of neutrophils, which is essential for their functions as the first responders in innate immunity. Nature Publishing Group UK 2022-03-28 2022 /pmc/articles/PMC8964420/ /pubmed/35347316 http://dx.doi.org/10.1038/s42255-022-00550-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Britt, Emily C. Lika, Jorgo Giese, Morgan A. Schoen, Taylor J. Seim, Gretchen L. Huang, Zhengping Lee, Pui Y. Huttenlocher, Anna Fan, Jing Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils |
title | Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils |
title_full | Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils |
title_fullStr | Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils |
title_full_unstemmed | Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils |
title_short | Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils |
title_sort | switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964420/ https://www.ncbi.nlm.nih.gov/pubmed/35347316 http://dx.doi.org/10.1038/s42255-022-00550-8 |
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