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Diverse stimuli engage different neutrophil extracellular trap pathways

Open access
Kenny, Elaine F, Herzig, Alf, Krüger, Renate, Muth, Aaron, Mondal, Santanu, Thompson, Paul R, Brinkmann, Volker, Bernuth, Horst von, Zychlinsky, Arturo·2017·eLife

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.

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Metadata

Authors
Kenny, E. F., Herzig, A., Krüger, R., Muth, A., Mondal, S., Thompson, P. R., Brinkmann, V., Bernuth, H. V., & Zychlinsky, A.
Venue
eLife
Published
2017-06-02
Volume
6
ISSN
2050-084X (ISSN-L)
OpenAlex
W2621393405
Cited by
797
References
8
FWCI
26.16
Type
journal article
Language
en
Open access
gold
Funders
  • Max-Planck-Gesellschaft
  • National Institutes of Health (GM118112)

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Kenny, E. F., Herzig, A., Krüger, R., Muth, A., Mondal, S., Thompson, P. R., Brinkmann, V., Bernuth, H. V., & Zychlinsky, A. (2017). Diverse stimuli engage different neutrophil extracellular trap pathways. eLife. https://doi.org/10.7554/elife.24437

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