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The impact of hypoxia on neutrophil degranulation and consequences for the host

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Title: The impact of hypoxia on neutrophil degranulation and consequences for the host
Authors: Lodge, KM
Cowburn, AS
Li, W
Condliffe, AM
Item Type: Journal Article
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.
Issue Date: 11-Feb-2020
Date of Acceptance: 8-Feb-2020
URI: http://hdl.handle.net/10044/1/82379
DOI: 10.3390/ijms21041183
ISSN: 1422-0067
Publisher: MDPI AG
Start Page: 1
End Page: 21
Journal / Book Title: International Journal of Molecular Sciences
Volume: 21
Issue: 4
Copyright Statement: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
Chemistry
neutrophils
hypoxia
degranulation
ENDOTHELIAL-GROWTH-FACTOR
WEIBEL-PALADE BODIES
PHOSPHOINOSITIDE 3-KINASE
INDUCIBLE FACTOR-1-ALPHA
STREPTOCOCCUS-PNEUMONIAE
PULMONARY-HYPERTENSION
BACTERICIDAL CAPACITY
INFLAMMATORY CELLS
SECRETORY VESICLES
MAMMALIAN TARGET
degranulation
hypoxia
neutrophils
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
Chemistry
neutrophils
hypoxia
degranulation
ENDOTHELIAL-GROWTH-FACTOR
WEIBEL-PALADE BODIES
PHOSPHOINOSITIDE 3-KINASE
INDUCIBLE FACTOR-1-ALPHA
STREPTOCOCCUS-PNEUMONIAE
PULMONARY-HYPERTENSION
BACTERICIDAL CAPACITY
INFLAMMATORY CELLS
SECRETORY VESICLES
MAMMALIAN TARGET
Chemical Physics
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Publication Status: Published
Article Number: ARTN 1183
Online Publication Date: 2020-02-11
Appears in Collections:National Heart and Lung Institute



This item is licensed under a Creative Commons License Creative Commons