ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation.
J Cell Biol
; 216(12): 4073-4090, 2017 12 04.
Article
em En
| MEDLINE
| ID: mdl-29150539
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto
/
Espécies Reativas de Oxigênio
/
Armadilhas Extracelulares
/
Glutationa
/
Neutrófilos
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Suíça
País de publicação:
Estados Unidos