| Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. | |
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MedLine Citation:
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PMID: 21060338 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neutrophil extracellular traps (NETs) are extracellular chromatin structures that can trap and degrade microbes. They arise from neutrophils that have activated a cell death program called NET cell death, or NETosis. Activation of NETosis has been shown to involve NADPH oxidase activity, disintegration of the nuclear envelope and most granule membranes, decondensation of nuclear chromatin and formation of NETs. We report that in phorbol myristate acetate (PMA)-stimulated neutrophils, intracellular chromatin decondensation and NET formation follow autophagy and superoxide production, both of which are required to mediate PMA-induced NETosis and occur independently of each other. Neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase activity, still exhibit PMA-induced autophagy. Conversely, PMA-induced NADPH oxidase activity is not affected by pharmacological inhibition of autophagy. Interestingly, inhibition of either autophagy or NADPH oxidase prevents intracellular chromatin decondensation, which is essential for NETosis and NET formation, and results in cell death characterized by hallmarks of apoptosis. These results indicate that apoptosis might function as a backup program for NETosis when autophagy or NADPH oxidase activity is prevented. |
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Authors:
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Quinten Remijsen; Tom Vanden Berghe; Ellen Wirawan; Bob Asselbergh; Eef Parthoens; Riet De Rycke; Sam Noppen; Michel Delforge; Jean Willems; Peter Vandenabeele |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-09 |
Journal Detail:
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Title: Cell research Volume: 21 ISSN: 1748-7838 ISO Abbreviation: Cell Res. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-03 Completed Date: 2011-05-19 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 9425763 Medline TA: Cell Res Country: China |
Other Details:
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Languages: eng Pagination: 290-304 Citation Subset: IM |
Affiliation:
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IRC - Laboratory of Biochemistry, Department of Medicine, KU Leuven Campus Kortrijk, Kortrijk, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis* Autophagy* Chromatin Assembly and Disassembly Granulomatous Disease, Chronic / metabolism Humans Membrane Glycoproteins / metabolism NADH, NADPH Oxidoreductases / metabolism NADPH Oxidase / metabolism Neutrophils / cytology, metabolism* Superoxides / metabolism* Tetradecanoylphorbol Acetate / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/CYBB protein, human; 0/Membrane Glycoproteins; 11062-77-4/Superoxides; 16561-29-8/Tetradecanoylphorbol Acetate; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.3.1/NADPH Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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