1. Immunology and Inflammation

Histone H3 clipping is a novel signature of human neutrophil extracellular traps

  1. Dorothea Ogmore Tilley
  2. Ulrike Abuabed
  3. Ursula Zimny Arndt
  4. Monika Schmid
  5. Stefan Florian
  6. Peter R Jungblut
  7. Volker Brinkmann
  8. Alf Herzig
  9. Arturo Zychlinsky  Is a corresponding author
  1. Max Planck Institute for Infection Biology, Germany
  2. Charité - Universitätsmedizin Berlin, Germany
https://doi.org/10.7554/eLife.68283
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Cite this article
  1. Dorothea Ogmore Tilley
  2. Ulrike Abuabed
  3. Ursula Zimny Arndt
  4. Monika Schmid
  5. Stefan Florian
  6. Peter R Jungblut
  7. Volker Brinkmann
  8. Alf Herzig
  9. Arturo Zychlinsky
(2022)
Histone H3 clipping is a novel signature of human neutrophil extracellular traps
eLife 11:e68283.
https://doi.org/10.7554/eLife.68283
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Abstract

Neutrophils are critical to host defence, executing diverse strategies to perform their antimicrobial and regulatory functions. One tactic is the production of neutrophil extracellular traps (NETs). In response to certain stimuli neutrophils decondense their lobulated nucleus and release chromatin into the extracellular space through a process called NETosis. However, NETosis, and the subsequent degradation of NETs, can become dysregulated. NETs are proposed to play a role in infectious as well as many non-infection related diseases including cancer, thrombosis, autoimmunity and neurological disease. Consequently, there is a need to develop specific tools for the study of these structures in disease contexts. In this study, we identified a NET-specific histone H3 cleavage event and harnessed this to develop a cleavage site-specific antibody for the detection of human NETs. By microscopy, this antibody distinguishes NETs from chromatin in purified and mixed cell samples. It also detects NETs in tissue sections. We propose this antibody as a new tool to detect and quantify NETs.

Data availability

Data generated or analysed during this study are included in the manuscript. Source data files have been provided.

Article and author information

Author details

  1. Dorothea Ogmore Tilley

    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    Dorothea Ogmore Tilley, has made a patent application for this antibody hybridoma cell line and sequence and its use in the detection of NETs outside of research purposes. No. EP 21 159 757.0.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3254-6991

  2. Ulrike Abuabed

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

  3. Ursula Zimny Arndt

    Protein Analysis Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.

  4. Monika Schmid

    Protein Analysis Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.

  5. Stefan Florian

    Institut für Pathologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.

  6. Peter R Jungblut

    Protein Analysis Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    No competing interests declared.

  7. Volker Brinkmann

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

  8. Alf Herzig

    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    Competing interests
    Alf Herzig, has made a patent application for this antibody hybridoma cell line and sequence and its use in the detection of NETs outside of research purposes. No. EP 21 159 757.0.

  9. Arturo Zychlinsky

    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    For correspondence
    zychlinsky@mpiib-berlin.mpg.de
    Competing interests
    Arturo Zychlinsky, has made a patent application for this antibody hybridoma cell line and sequence and its use in the detection of NETs outside of research purposes. No. EP 21 159 757.0.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6018-193X

Funding

Max Planck Institute for Infection Biology

  • Arturo Zychlinsky

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Carla V Rothlin, Yale University, United States

Ethics

Human subjects: Samples were collected from healthy donors who had provided informed consent according to the Declaration of Helsinki. Ethical approval was provided by the ethics committee of Charité-Universitätsmedizin Berlin and blood was donated anonymously at Charité Hospital Berlin. For histological tissue samples, tissue was obtained from historical archives and used in an anonymised way after approval through the Charité Ethics Committee (Project EA4/124/19, July 24, 2019). Informed consent from patients for use of biomaterials for research was obtained as part of the institutional treatment contract at Charité.

Version history

  1. Received: March 10, 2021
  2. Preprint posted: March 16, 2021 (view preprint)
  3. Accepted: October 24, 2022
  4. Accepted Manuscript published: October 25, 2022 (version 1)
  5. Version of Record published: November 15, 2022 (version 2)

Copyright

© 2022, Tilley 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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  1. Dorothea Ogmore Tilley
  2. Ulrike Abuabed
  3. Ursula Zimny Arndt
  4. Monika Schmid
  5. Stefan Florian
  6. Peter R Jungblut
  7. Volker Brinkmann
  8. Alf Herzig
  9. Arturo Zychlinsky
(2022)
Histone H3 clipping is a novel signature of human neutrophil extracellular traps
eLife 11:e68283.
https://doi.org/10.7554/eLife.68283

Share this article

https://doi.org/10.7554/eLife.68283

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