Sadiku, P., Willson, J.A., Ryan, E.M. et al. (33 more authors) (2021) Neutrophils fuel effective immune responses through gluconeogenesis and glycogenesis. Cell Metabolism, 33 (2). 411-423.e4. ISSN 1550-4131
Abstract
Neutrophils can function and survive in injured and infected tissues, where oxygen and metabolic substrates are limited. Using radioactive flux assays and LC-MS tracing with U-13C glucose, glutamine, and pyruvate, we observe that neutrophils require the generation of intracellular glycogen stores by gluconeogenesis and glycogenesis for effective survival and bacterial killing. These metabolic adaptations are dynamic, with net increases in glycogen stores observed following LPS challenge or altitude-induced hypoxia. Neutrophils from patients with chronic obstructive pulmonary disease have reduced glycogen cycling, resulting in impaired function. Metabolic specialization of neutrophils may therefore underpin disease pathology and allow selective therapeutic targeting.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | neutrophil; glycogenesis; gluconeogenesis; inflammation; COPD; glycogen; glycolysis; glycogenolysis; GYS1 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number ACADEMY OF MEDICAL SCIENCES nan |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Dec 2020 12:34 |
Last Modified: | 01 Feb 2022 12:20 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.cmet.2020.11.016 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:169130 |