Diverse stimuli engage different neutrophil extracellular trap pathways
- Max Planck Institute for Infection Biology, Germany
- Charité Medical School, Germany
- University of Massachusetts Medical School, United States
- Cited 128
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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.
Article and author information
Author details
Funding
Max-Planck-Gesellschaft
- Elaine F Kenny
- Alf Herzig
- Arturo Zychlinsky
National Institutes of Health (GM118112)
- Aaron Muth
- Santanu Mondal
- Paul R Thompson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Blood samples were collected according to the Declaration of Helsinki with study participants providing written informed consent. All samples were collected with approval from the ethics committee-Charité -Universitätsmedizin Berlin.
Reviewing Editor
- Axel A Brakhage, Friedrich Schiller University Jena and Hans-Knöll-Institut, Germany
Publication history
- Received: December 20, 2016
- Accepted: June 1, 2017
- Accepted Manuscript published: June 2, 2017 (version 1)
- Version of Record published: July 4, 2017 (version 2)
Copyright
© 2017, Kenny et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Cell Biology
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- Cell Biology
- Chromosomes and Gene Expression
