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ResearchIn-Press PreviewInflammationMetabolism Free access | 10.1172/JCI134073
1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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Morrison, T.
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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1Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
2Division of Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
3Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
4Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Centre, Leuven, Belgium
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Published April 6, 2021 - More info
Limiting dysfunctional neutrophilic inflammation whilst 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 labelled amino acids into metabolic enzymes, pro-inflammatory 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 hypoglycaemia, characteristic of inflamed tissues, promoted this extra-cellular 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 which enable neutrophils to sustain synthetic and effector functions in the tissues.