| Hypoxia selectively inhibits respiratory burst activity and killing of Staphylococcus aureus in human neutrophils. | |
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MedLine Citation:
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PMID: 21135168 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neutrophils play a central role in the innate immune response and a critical role in bacterial killing. Most studies of neutrophil function have been conducted under conditions of ambient oxygen, but inflamed sites where neutrophils operate may be extremely hypoxic. Previous studies indicate that neutrophils sense and respond to hypoxia via the ubiquitous prolyl hydroxylase/hypoxia-inducible factor pathway and that this can signal for enhanced survival. In the current study, human neutrophils were shown to upregulate hypoxia-inducible factor (HIF)-1α-dependent gene expression under hypoxic incubation conditions (3 kPa), with a consequent substantial delay in the onset of apoptosis. Despite this, polarization and chemotactic responsiveness to IL-8 and fMLP were entirely unaffected by hypoxia. Similarly, hypoxia did not diminish the ability of neutrophils to phagocytose serum-opsonized heat-killed streptococci. Of the secretory functions examined, IL-8 generation was preserved and elastase release was enhanced by hypoxia. Hypoxia did, however, cause a major reduction in respiratory burst activity induced both by the soluble agonist fMLP and by ingestion of opsonized zymosan, without affecting expression of the NADPH oxidase subunits. Critically, this reduction in respiratory burst activity under hypoxia was associated with a significant defect in the killing of Staphylococcus aureus. In contrast, killing of Escherichia coli, which is predominantly oxidase independent, was fully preserved under hypoxia. In conclusion, these studies suggest that although the NADPH oxidase-dependent bacterial killing mechanism may be compromised by hypoxia, neutrophils overall appear extremely well adapted to operate successfully under severely hypoxic conditions. |
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Authors:
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Naomi N McGovern; Andrew S Cowburn; Linsey Porter; Sarah R Walmsley; Charlotte Summers; Alfred A R Thompson; Sadia Anwar; Lisa C Willcocks; Moira K B Whyte; Alison M Condliffe; Edwin R Chilvers |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-12-06 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 186 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-21 Completed Date: 2011-01-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 453-63 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blood Bactericidal Activity
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immunology* Cell Degranulation / immunology Cell Hypoxia / immunology Cells, Cultured Chemotaxis, Leukocyte / immunology Humans Leukocyte Elastase / secretion N-Formylmethionine Leucyl-Phenylalanine / pharmacology NADPH Oxidase / antagonists & inhibitors, blood, physiology Neutrophils / enzymology, immunology*, metabolism, microbiology* Reactive Oxygen Species / antagonists & inhibitors, blood Receptors, Immunologic / blood, metabolism Respiratory Burst / immunology* Staphylococcus aureus / growth & development*, immunology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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//Medical Research Council; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; 0/Receptors, Immunologic; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; EC 1.6.3.1/NADPH Oxidase; EC 3.4.21.37/Leukocyte Elastase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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