ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation
Open accessAbstract
The antimicrobial defense activity of neutrophils partly depends on their ability to form neutrophil extracellular traps (NETs), but the underlying mechanism controlling NET formation remains unclear. We demonstrate that inhibiting cytoskeletal dynamics with pharmacological agents or by genetic manipulation prevents the degranulation of neutrophils and mitochondrial DNA release required for NET formation. Wiskott-Aldrich syndrome protein–deficient neutrophils are unable to polymerize actin and exhibit a block in both degranulation and DNA release. Similarly, neutrophils with a genetic defect in NADPH oxidase fail to induce either actin and tubulin polymerization or NET formation on activation. Moreover, neutrophils deficient in glutaredoxin 1 (Grx1), an enzyme required for deglutathionylation of actin and tubulin, are unable to polymerize either cytoskeletal network and fail to degranulate or release DNA. Collectively, cytoskeletal dynamics are achieved as a balance between reactive oxygen species–regulated effects on polymerization and glutathionylation on the one hand and the Grx1-mediated deglutathionylation that is required for NET formation on the other.
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Recent findings indicate ROS drive NET extrusion by a mechanism requiring an intact cytoskeleton.
“recent findings indicate that ROS drive NET extrusion by a mechanism that requires an intact cytoskeleton [743].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [743]
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- Authors
- Stojkov, D., Amini, P., Oberson, K., Sokollik, C., Duppenthaler, A., Simon, H.-U., & Yousefi, S.
- Affiliations
- University of Bern (CH)
- University Children’s Hospital Bern (CH)
- Institute of Pharmacology, University of Bern, Bern, Switzerland 1
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2017-11-17
- Volume
- 216
- Issue
- 12
- Pages
- 4073-4090
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC5716265
- OpenAlex
- W2769698474
- Cited by
- 142
- References
- 60
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 11 · 2023: 13 · 2022: 22 · 2021: 23 · 2020: 15 · 2019: 21 · 2018: 11
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, cc-by-nc-sa)
- Open Access CRIS of the University of Bern
- Funders
- Swiss National Science Foundation (31003A_173215, 310030_166473)
- University of Bern
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Keywords
- neutrophil extracellular traps, reactive oxygen species, glutathionylation, deglutathionylation, glutaredoxin 1, cytoskeletal dynamics, actin polymerization, microtubule assembly, neutrophil degranulation, mitochondrial DNA release, Wiskott-Aldrich syndrome protein, NADPH oxidase
- MeSH terms
- Actins, Animals, Cytoskeleton, DNA, Mitochondrial, Gene Expression Regulation, Glutathione, Humans, Mice, Transgenic, Neutrophils, Oxidation-Reduction, Tubulin, Signal Transduction, Cell Degranulation, Granulocyte-Macrophage Colony-Stimulating Factor, Reactive Oxygen Species, Homeodomain Proteins, NADPH Oxidases, Wiskott-Aldrich Syndrome Protein, Mice, Glutaredoxins, Primary Cell Culture, Extracellular Traps
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