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ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation
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 mani...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716265/ https://www.ncbi.nlm.nih.gov/pubmed/29150539 http://dx.doi.org/10.1083/jcb.201611168 |
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author | Stojkov, Darko Amini, Poorya Oberson, Kevin Sokollik, Christiane Duppenthaler, Andrea Simon, Hans-Uwe Yousefi, Shida |
author_facet | Stojkov, Darko Amini, Poorya Oberson, Kevin Sokollik, Christiane Duppenthaler, Andrea Simon, Hans-Uwe Yousefi, Shida |
author_sort | Stojkov, Darko |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5716265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57162652018-06-04 ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation Stojkov, Darko Amini, Poorya Oberson, Kevin Sokollik, Christiane Duppenthaler, Andrea Simon, Hans-Uwe Yousefi, Shida J Cell Biol Research Articles 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. The Rockefeller University Press 2017-12-04 /pmc/articles/PMC5716265/ /pubmed/29150539 http://dx.doi.org/10.1083/jcb.201611168 Text en © 2017 Stojkov et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Stojkov, Darko Amini, Poorya Oberson, Kevin Sokollik, Christiane Duppenthaler, Andrea Simon, Hans-Uwe Yousefi, Shida ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation |
title | ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation |
title_full | ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation |
title_fullStr | ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation |
title_full_unstemmed | ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation |
title_short | ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation |
title_sort | ros and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716265/ https://www.ncbi.nlm.nih.gov/pubmed/29150539 http://dx.doi.org/10.1083/jcb.201611168 |
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