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Histone Acetylation Promotes Neutrophil Extracellular Trap Formation

Neutrophils undergo a unique form of cell death to generate neutrophil extracellular traps (NETs). It is well established that citrullination of histones (e.g., CitH3) facilitates chromatin decondensation during NET formation (NETosis), particularly during calcium-induced NETosis that is independent...

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Autores principales: Hamam, Hussein J., Khan, Meraj A., Palaniyar, Nades
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359456/
https://www.ncbi.nlm.nih.gov/pubmed/30669408
http://dx.doi.org/10.3390/biom9010032
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author Hamam, Hussein J.
Khan, Meraj A.
Palaniyar, Nades
author_facet Hamam, Hussein J.
Khan, Meraj A.
Palaniyar, Nades
author_sort Hamam, Hussein J.
collection PubMed
description Neutrophils undergo a unique form of cell death to generate neutrophil extracellular traps (NETs). It is well established that citrullination of histones (e.g., CitH3) facilitates chromatin decondensation during NET formation (NETosis), particularly during calcium-induced NETosis that is independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation. However, the importance of other forms of histone modifications in NETosis has not been established. We considered that acetylation of histones would also facilitate NETosis. To test this hypothesis, we induced NOX-dependent NETosis in human neutrophils with phorbol myristate acetate or lipopolysaccharide (from Escherichia coli 0128), and NOX-independent NETosis with calcium ionophores A23187 or ionomycin (from Streptomyces conglobatus) in the presence or absence of two pan histone deacetylase inhibitors (HDACis), belinostat and panobinostat (within their half maximal inhibitory concentration (IC50) range). The presence of these inhibitors increased histone acetylation (e.g., AcH4) in neutrophils. Histone acetylation was sufficient to cause a significant increase (~20%) in NETosis in resting neutrophils above baseline values. When acetylation was promoted during NOX-dependent or -independent NETosis, the degree of NETosis additively increased (~15–30%). Reactive oxygen species (ROS) production is essential for baseline NETosis (mediated either by NOX or mitochondria); however, HDACis did not promote ROS production. The chromatin decondensation step requires promoter melting and transcriptional firing in both types of NETosis; consistent with this point, suppression of transcription prevented the NETosis induced by the acetylation of histones. Collectively, this study establishes that histone acetylation (e.g., AcH4) promotes NETosis at baseline, and when induced by both NOX-dependent or -independent pathway agonists, in human neutrophils. Therefore, we propose that acetylation of histone is a key component of NETosis.
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spelling pubmed-63594562019-02-11 Histone Acetylation Promotes Neutrophil Extracellular Trap Formation Hamam, Hussein J. Khan, Meraj A. Palaniyar, Nades Biomolecules Article Neutrophils undergo a unique form of cell death to generate neutrophil extracellular traps (NETs). It is well established that citrullination of histones (e.g., CitH3) facilitates chromatin decondensation during NET formation (NETosis), particularly during calcium-induced NETosis that is independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation. However, the importance of other forms of histone modifications in NETosis has not been established. We considered that acetylation of histones would also facilitate NETosis. To test this hypothesis, we induced NOX-dependent NETosis in human neutrophils with phorbol myristate acetate or lipopolysaccharide (from Escherichia coli 0128), and NOX-independent NETosis with calcium ionophores A23187 or ionomycin (from Streptomyces conglobatus) in the presence or absence of two pan histone deacetylase inhibitors (HDACis), belinostat and panobinostat (within their half maximal inhibitory concentration (IC50) range). The presence of these inhibitors increased histone acetylation (e.g., AcH4) in neutrophils. Histone acetylation was sufficient to cause a significant increase (~20%) in NETosis in resting neutrophils above baseline values. When acetylation was promoted during NOX-dependent or -independent NETosis, the degree of NETosis additively increased (~15–30%). Reactive oxygen species (ROS) production is essential for baseline NETosis (mediated either by NOX or mitochondria); however, HDACis did not promote ROS production. The chromatin decondensation step requires promoter melting and transcriptional firing in both types of NETosis; consistent with this point, suppression of transcription prevented the NETosis induced by the acetylation of histones. Collectively, this study establishes that histone acetylation (e.g., AcH4) promotes NETosis at baseline, and when induced by both NOX-dependent or -independent pathway agonists, in human neutrophils. Therefore, we propose that acetylation of histone is a key component of NETosis. MDPI 2019-01-18 /pmc/articles/PMC6359456/ /pubmed/30669408 http://dx.doi.org/10.3390/biom9010032 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hamam, Hussein J.
Khan, Meraj A.
Palaniyar, Nades
Histone Acetylation Promotes Neutrophil Extracellular Trap Formation
title Histone Acetylation Promotes Neutrophil Extracellular Trap Formation
title_full Histone Acetylation Promotes Neutrophil Extracellular Trap Formation
title_fullStr Histone Acetylation Promotes Neutrophil Extracellular Trap Formation
title_full_unstemmed Histone Acetylation Promotes Neutrophil Extracellular Trap Formation
title_short Histone Acetylation Promotes Neutrophil Extracellular Trap Formation
title_sort histone acetylation promotes neutrophil extracellular trap formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359456/
https://www.ncbi.nlm.nih.gov/pubmed/30669408
http://dx.doi.org/10.3390/biom9010032
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