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Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation

Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin DNA and contents of granules, such as myeloperoxidase (MPO) and neutrophil elastase (NE). NETs are usually released from neutrophils undergoing NETosis, a neutrophil-specific cell death mode characteriz...

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Autores principales: Tokuhiro, Takuto, Ishikawa, Akane, Sato, Haruka, Takita, Shunya, Yoshikawa, Ayuri, Anzai, Ryoko, Sato, Shinichi, Aoyagi, Ryohei, Arita, Makoto, Shibuya, Takumi, Aratani, Yasuaki, Shimizu, Shigeomi, Tanaka, Masato, Yotsumoto, Satoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458647/
https://www.ncbi.nlm.nih.gov/pubmed/34568331
http://dx.doi.org/10.3389/fcell.2021.718586
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author Tokuhiro, Takuto
Ishikawa, Akane
Sato, Haruka
Takita, Shunya
Yoshikawa, Ayuri
Anzai, Ryoko
Sato, Shinichi
Aoyagi, Ryohei
Arita, Makoto
Shibuya, Takumi
Aratani, Yasuaki
Shimizu, Shigeomi
Tanaka, Masato
Yotsumoto, Satoshi
author_facet Tokuhiro, Takuto
Ishikawa, Akane
Sato, Haruka
Takita, Shunya
Yoshikawa, Ayuri
Anzai, Ryoko
Sato, Shinichi
Aoyagi, Ryohei
Arita, Makoto
Shibuya, Takumi
Aratani, Yasuaki
Shimizu, Shigeomi
Tanaka, Masato
Yotsumoto, Satoshi
author_sort Tokuhiro, Takuto
collection PubMed
description Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin DNA and contents of granules, such as myeloperoxidase (MPO) and neutrophil elastase (NE). NETs are usually released from neutrophils undergoing NETosis, a neutrophil-specific cell death mode characterized by the collapse and disappearance of cell membranes and nuclear envelopes. It is well known that production of reactive oxygen species (ROS) triggers NETosis and NET formation. However, details of intracellular signaling downstream of ROS production during NETosis and NET formation remains uncertain. Here, we demonstrated that the peroxidation of phospholipids plays a critical role in NETosis and NET formation induced by phorbol 12-myristate13-acetate (PMA) or immune complex in vitro and by lipopolysaccharide (LPS) in vivo. This phospholipid peroxidation is mediated by the enzymatic activity of MPO. On the other hand, NE, which was previously reported to be released from granules to cytosol by MPO during NET formation, is not required for either the peroxidation of phospholipids or the execution of NETosis, but contributes to chromatin decondensation and nuclear swelling independently of MPO-mediated oxidized phospholipids. Analysis of isolated nuclei clearly demonstrated that oxidized phospholipids and NE differently yet synergistically execute chromatin decondensation and nuclear swelling, and the subsequent release of nuclear contents. These findings indicate the dual roles of MPO in NETosis and NET formation, and provide new insight into the molecular mechanism of these phenomena.
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spelling pubmed-84586472021-09-24 Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation Tokuhiro, Takuto Ishikawa, Akane Sato, Haruka Takita, Shunya Yoshikawa, Ayuri Anzai, Ryoko Sato, Shinichi Aoyagi, Ryohei Arita, Makoto Shibuya, Takumi Aratani, Yasuaki Shimizu, Shigeomi Tanaka, Masato Yotsumoto, Satoshi Front Cell Dev Biol Cell and Developmental Biology Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin DNA and contents of granules, such as myeloperoxidase (MPO) and neutrophil elastase (NE). NETs are usually released from neutrophils undergoing NETosis, a neutrophil-specific cell death mode characterized by the collapse and disappearance of cell membranes and nuclear envelopes. It is well known that production of reactive oxygen species (ROS) triggers NETosis and NET formation. However, details of intracellular signaling downstream of ROS production during NETosis and NET formation remains uncertain. Here, we demonstrated that the peroxidation of phospholipids plays a critical role in NETosis and NET formation induced by phorbol 12-myristate13-acetate (PMA) or immune complex in vitro and by lipopolysaccharide (LPS) in vivo. This phospholipid peroxidation is mediated by the enzymatic activity of MPO. On the other hand, NE, which was previously reported to be released from granules to cytosol by MPO during NET formation, is not required for either the peroxidation of phospholipids or the execution of NETosis, but contributes to chromatin decondensation and nuclear swelling independently of MPO-mediated oxidized phospholipids. Analysis of isolated nuclei clearly demonstrated that oxidized phospholipids and NE differently yet synergistically execute chromatin decondensation and nuclear swelling, and the subsequent release of nuclear contents. These findings indicate the dual roles of MPO in NETosis and NET formation, and provide new insight into the molecular mechanism of these phenomena. Frontiers Media S.A. 2021-09-09 /pmc/articles/PMC8458647/ /pubmed/34568331 http://dx.doi.org/10.3389/fcell.2021.718586 Text en Copyright © 2021 Tokuhiro, Ishikawa, Sato, Takita, Yoshikawa, Anzai, Sato, Aoyagi, Arita, Shibuya, Aratani, Shimizu, Tanaka and Yotsumoto. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Tokuhiro, Takuto
Ishikawa, Akane
Sato, Haruka
Takita, Shunya
Yoshikawa, Ayuri
Anzai, Ryoko
Sato, Shinichi
Aoyagi, Ryohei
Arita, Makoto
Shibuya, Takumi
Aratani, Yasuaki
Shimizu, Shigeomi
Tanaka, Masato
Yotsumoto, Satoshi
Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation
title Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation
title_full Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation
title_fullStr Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation
title_full_unstemmed Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation
title_short Oxidized Phospholipids and Neutrophil Elastase Coordinately Play Critical Roles in NET Formation
title_sort oxidized phospholipids and neutrophil elastase coordinately play critical roles in net formation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458647/
https://www.ncbi.nlm.nih.gov/pubmed/34568331
http://dx.doi.org/10.3389/fcell.2021.718586
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