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Diverse stimuli engage different neutrophil extracellular trap pathways
Open accessAbstract
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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Neutrophil Extracellular Traps Kill Bacteria
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“The generation of oxidants by MPO liberates NE from the azurosome, allowing it to translocate to the nucleus where it aids in the decondensation of the chromatin by proteolyzing histones (Metzler et al., 2014).”
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Self-citationK+ regulates Ca2+ to drive inflammasome signaling: dynamic visualization of ion flux in live cells
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“A23187 is a calcium ionophore that causes a massive influx of calcium and nigericin stimulates potassium effluxes in cells which also results in the influx of calcium demonstrating the similarity between the ionophores in their mechanism of NET induction (Yaron et al., 2015).”
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Gasdermin D plays a vital role in the generation of neutrophil extracellular traps
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Self-citationNoncanonical inflammasome signaling elicits gasdermin D–dependent neutrophil extracellular traps
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NETosis: Molecular Mechanisms, Role in Physiology and Pathology
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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
- Publisher
- eLife Sciences Publications, Ltd
- 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
- Licence
- creativecommons.org/licenses/by/4.0/ (vor)
- creativecommons.org/licenses/by/4.0/ (am)
- creativecommons.org/licenses/by/4.0/ (tdm)
- Funders
- Max-Planck-Gesellschaft
- National Institutes of Health (GM118112)
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