Histone H3 clipping is a novel signature of human neutrophil extracellular traps
- Max Planck Institute for Infection Biology, Germany
- Charité - Universitätsmedizin Berlin, Germany
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
Dorothea Ogmore Tilley
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.
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.
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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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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