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 (2017). ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation. Journal of cell biology, 216(12), pp. 4073-4090. Rockefeller University Press 10.1083/jcb.201611168

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Stojkov, Darko; Oberson, Kevin; Sokollik, Christiane; Duppenthaler, Andrea; Simon, Hans-Uwe and Yousefi, Shida

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0021-9525

Publisher:

Rockefeller University Press

Language:

English

Submitter:

Jana Berger

Date Deposited:

25 Jan 2018 14:56

Last Modified:

24 Oct 2019 20:22

Publisher DOI:

10.1083/jcb.201611168

PubMed ID:

29150539

BORIS DOI:

10.7892/boris.108072

URI:

https://boris.unibe.ch/id/eprint/108072

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