Cited by 818Neutrophil, Myeloperoxidase and Oxidative MechanismsCell death mechanisms and regulationAntimicrobial Peptides and Activities

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Neutrophil extracellular trap cell death requires both autophagy and superoxide generation

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Remijsen, Quinten, Berghe, Tom Vanden, Wirawan, Ellen, Asselbergh, Bob, Parthoens, Eef, De Rycke, Riet, Noppen, Sam, Delforge, Michel, Willems, Jean, Vandenabeele, Peter·2011·Cell Research

DOI 10.1038/cr.2010.150PMC PMC3193439

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Abstract

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: Remijsen, Q., Berghe, T. V., Wirawan, E., Asselbergh, B., Parthoens, E., De Rycke, R., Noppen, S., Delforge, M., Willems, J., & Vandenabeele, P.
Affiliations: KU Leuven (BE)
Ghent University (BE)
Universitair Ziekenhuis Leuven (BE)
Corresponding author: Willems, Jean
Vandenabeele, Peter
ORCID: Berghe, Tom Vanden
Asselbergh, Bob
Noppen, Sam
Delforge, Michel
Vandenabeele, Peter
Venue: Cell Research
Publisher: Springer Science and Business Media LLC
Published: 2010-11-09
Volume: 21
Issue: 2
Pages: 290-304
ISSN: 1001-0602 (ISSN-L)
1748-7838
DOI: 10.1038/cr.2010.150
PMC: PMC3193439
OpenAlex: W2091512988
Cited by: 818
References: 51
Citations by year: 2026: 32 · 2025: 58 · 2024: 50 · 2023: 54 · 2022: 48 · 2021: 68 · 2020: 57 · 2019: 87 · 2018: 56 · 2017: 73 · 2016: 62 · 2015: 49 · 2014: 40 · 2013: 39 · 2012: 31
FWCI: 11.55
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: public-domain
www.springer.com/tdm (tdm)
Locations: Cell Research (publishedVersion, public-domain)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Funders: European Commission (200767)
Universiteit Gent (01M00709)
Vlaams Instituut voor Biotechnologie (BOF09/01M00709)
Vlaamse regering (BOF09/01M00709)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
Keywords: neutrophil extracellular traps, NETosis, autophagy, superoxide, NADPH oxidase, chromatin decondensation, neutrophil cell death, apoptosis, chronic granulomatous disease, phorbol myristate acetate, innate immunity
MeSH terms: NADPH Oxidase 2, Autophagy, Granulomatous Disease, Chronic, Humans, Membrane Glycoproteins, NADH, NADPH Oxidoreductases, Neutrophils, Superoxides, Tetradecanoylphorbol Acetate, Apoptosis, NADPH Oxidases, Chromatin Assembly and Disassembly

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Neutrophil extracellular trap cell death requires both autophagy and superoxide generation

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