UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

6-2-2017

Document Type

Article Postprint

Disciplines

Biochemistry | Cell Biology | Enzymes and Coenzymes | Immunology and Infectious Disease | Medicinal-Pharmaceutical Chemistry | Therapeutics

Abstract

Neutrophils release neutrophil extracellular traps (NETs) which ensnare pathogens and have pathogenic functions in diverse diseases. We examined the NETosis pathways induced by five stimuli; PMA, the calcium ionophore A23187, nigericin, Candida albicans and Group B Streptococcus. We studied NET production in neutrophils from healthy donors with inhibitors of molecules crucial to PMA induced NETs including protein kinase C, calcium, reactive oxygen species, the enzymes myeloperoxidase (MPO) and neutrophil elastase. Additionally, neutrophils from chronic granulomatous disease patients, carrying mutations in the NADPH oxidase complex or a MPO-deficient patient were examined. We show that PMA, C. albicans and GBS use a related pathway for NET induction whereas ionophores require an alternative pathway but that NETs produced by all stimuli are proteolytically active, kill bacteria and composed mainly of chromosomal DNA. Thus, we demonstrate that NETosis occurs through several signalling mechanisms, suggesting that extrusion of NETs is important in host defence.

Rights and Permissions

© 2017, Kenny et al. Citation: Elife. 2017 Jun 2;6. pii: e24437. doi: 10.7554/eLife.24437. [Epub ahead of print] Link to article on publisher's website

Related Resources

Link to article in PubMed

Keywords

cell biology, human, immunology

PubMed ID

28574339

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

 
 

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