Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism.

Autor:	Watts ER; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Howden AJ; Division of Cell Signaling and Immunology, University of Dundee, Dundee, United Kingdom., Morrison T; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Sadiku P; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Hukelmann J; Division of Cell Signaling and Immunology, University of Dundee, Dundee, United Kingdom., von Kriegsheim A; Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh, United Kingdom., Ghesquiere B; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium., Murphy F; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Mirchandani AS; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Humphries DC; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Grecian R; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Ryan EM; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Coelho P; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Blanco GR; Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh, United Kingdom., Plant TM; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Dickinson RS; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Finch A; Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, Edinburgh, United Kingdom., Vermaelen W; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium., Cantrell DA; Division of Cell Signaling and Immunology, University of Dundee, Dundee, United Kingdom., Whyte MK; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom., Walmsley SR; University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2021 May 17; Vol. 131 (10).
DOI:	10.1172/JCI134073
Abstrakt:	Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues.
Databáze:	MEDLINE
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