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The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host

1
Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
2
Department of Medicine, University of Cambridge, Cambridge CB2 0SP, UK
3
Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield, Sheffield S10 2RX, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1183; https://doi.org/10.3390/ijms21041183
Received: 13 January 2020 / Revised: 6 February 2020 / Accepted: 8 February 2020 / Published: 11 February 2020
(This article belongs to the Special Issue The Impact of Hypoxia on Neutrophil Signaling and Function)
Neutrophils are key effector cells of innate immunity, rapidly recruited to defend the host against invading pathogens. Neutrophils may kill pathogens intracellularly, following phagocytosis, or extracellularly, by degranulation and the release of neutrophil extracellular traps; all of these microbicidal strategies require the deployment of cytotoxic proteins and proteases, packaged during neutrophil development within cytoplasmic granules. Neutrophils operate in infected and inflamed tissues, which can be profoundly hypoxic. Neutrophilic infiltration of hypoxic tissues characterises a myriad of acute and chronic infectious and inflammatory diseases, and as well as potentially protecting the host from pathogens, neutrophil granule products have been implicated in causing collateral tissue damage in these scenarios. This review discusses the evidence for the enhanced secretion of destructive neutrophil granule contents observed in hypoxic environments and the potential mechanisms for this heightened granule exocytosis, highlighting implications for the host. Understanding the dichotomy of the beneficial and detrimental consequences of neutrophil degranulation in hypoxic environments is crucial to inform potential neutrophil-directed therapeutics in order to limit persistent, excessive, or inappropriate inflammation. View Full-Text
Keywords: neutrophils; hypoxia; degranulation neutrophils; hypoxia; degranulation
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MDPI and ACS Style

Lodge, K.M.; Cowburn, A.S.; Li, W.; Condliffe, A.M. The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host. Int. J. Mol. Sci. 2020, 21, 1183. https://doi.org/10.3390/ijms21041183

AMA Style

Lodge KM, Cowburn AS, Li W, Condliffe AM. The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host. International Journal of Molecular Sciences. 2020; 21(4):1183. https://doi.org/10.3390/ijms21041183

Chicago/Turabian Style

Lodge, Katharine M.; Cowburn, Andrew S.; Li, Wei; Condliffe, Alison M. 2020. "The Impact of Hypoxia on Neutrophil Degranulation and Consequences for the Host" Int. J. Mol. Sci. 21, no. 4: 1183. https://doi.org/10.3390/ijms21041183

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