1. Cell Biology
  2. Immunology and Inflammation
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Diverse stimuli engage different neutrophil extracellular trap pathways

  1. Elaine F Kenny  Is a corresponding author
  2. Alf Herzig
  3. Renate Krüger
  4. Aaron Muth
  5. Santanu Mondal
  6. Paul R Thompson
  7. Volker Brinkmann
  8. Horst Von Bernuth
  9. Arturo Zychlinsky
  1. Max Planck Institute for Infection Biology, Germany
  2. Charité Medical School, Germany
  3. University of Massachusetts Medical School, United States
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Cite this article as: eLife 2017;6:e24437 doi: 10.7554/eLife.24437

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

  1. Elaine F Kenny

    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    For correspondence
    kenny@mpiib-berlin.mpg.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9985-5620
  2. Alf Herzig

    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.
  3. Renate Krüger

    Department of Paediatric Pneumology and Immunology, Outpatient Clinic for Primary Immunodeficiencies, Charité Medical School, Berlin, Germany
    Competing interests
    No competing interests declared.
  4. Aaron Muth

    Department of Biochemistry and Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0646-9964
  5. Santanu Mondal

    Department of Biochemistry and Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  6. Paul R Thompson

    Department of Biochemistry and Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    Paul R Thompson, P.R.T. is a consultant to Bristol-Myers Squibb..
  7. Volker Brinkmann

    Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.
  8. Horst Von Bernuth

    Department of Paediatric Pneumology and Immunology, Outpatient Clinic for Primary Immunodeficiencies, Charité Medical School, Berlin, Germany
    Competing interests
    No competing interests declared.
  9. Arturo Zychlinsky

    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.

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

  1. Axel A Brakhage, Friedrich Schiller University Jena and Hans-Knöll-Institut, Germany

Publication history

  1. Received: December 20, 2016
  2. Accepted: June 1, 2017
  3. Accepted Manuscript published: June 2, 2017 (version 1)
  4. 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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