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The responses of macrophages in interaction with neutrophils that undergo NETosis

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Title: The responses of macrophages in interaction with neutrophils that undergo NETosis
Authors: Nakazawa, Daigo Browse this author
Shida, Haruki Browse this author
Kusunoki, Yoshihiro Browse this author
Miyoshi, Arina Browse this author
Nishio, Saori Browse this author →KAKEN DB
Tomaru, Utano Browse this author →KAKEN DB
Atsumi, Tatsuya Browse this author →KAKEN DB
Ishizu, Akihiro Browse this author →KAKEN DB
Keywords: Neutrophil extracellular traps
Extracellular DNA
Issue Date: Feb-2016
Publisher: Elsevier
Journal Title: Journal of autoimmunity
Volume: 67
Start Page: 19
End Page: 28
Publisher DOI: 10.1016/j.jaut.2015.08.018
PMID: 26347075
Abstract: Neutrophil extracellular traps (NETs) are net-like chromatin fibers decorated with antimicrobial proteins, which are released from dying neutrophils. The death of neutrophils with NET formation is called NETosis. Although NETs play important roles in the innate immunity, especially in the elimination of microbes, the extracellular release of DNA and intra-cytoplasmic/nuclear proteins can, on the other hand, result in diverse adversities to the hosts. Therefore, NETosis is adequately regulated in vivo. Currently, two mechanisms, namely DNase I-dependent digestion and phagocytosis by macrophages, have been shown as such regulatory mechanisms. In this study, we focused on the interaction of macrophages and neutrophils that underwent NETosis. Results demonstrated that macrophages displayed a phenotype dependent response after degradation of NETs. Several hours after the interaction, M2 macrophages induced a pro-inflammatory response, while M1 macrophages underwent cell death with nuclear decondensation. This nuclear decondensation of M1 macrophages occurred in a peptidylarginine deiminase 4-dependent manner and resulted in a local release of extracellular DNA. Thereafter, M1 macrophages degraded DNA derived from themselves in a caspase-activated DNase-dependent manner resulting in the clearance of extracellular DNA within 24 h. This transient increase and subsequent clearance mechanism of extracellular DNA seems very reasonable in terms of the double-edged sword-like property of NETs. The collective findings demonstrate a novel phenotype- and time-dependent regulation of NETosis by macrophages. (C) 2015 The Authors. Published by Elsevier Ltd.
Rights: ©2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article
Appears in Collections:保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石津 明洋

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