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

Published version
Peer-reviewed

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Authors

Lodge 
Cowburn 
Li 
Condliffe 

Abstract

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.

Description

Keywords

neutrophils, hypoxia, degranulation

Journal Title

International Journal of Molecular Sciences

Conference Name

Journal ISSN

1422-0067

Volume Title

21

Publisher

MDPI
Sponsorship
Medical Research Council (MR/No2995X/1)
BMA Foundation for Medical Research (Josephine Lansdell 2017)