Phorbol 12-myristate 13-acetate stimulation under hypoxia induces nuclear swelling with DNA outflow but not extracellular trap formation of neutrophils

Masuda, Sakiko; Kato, Kurumi; Ishibashi, Misato; Nishibata, Yuka; Sugimoto, Ayako; Nakazawa, Daigo; Tanaka, Satoshi; Tomaru, Utano; Tsujino, Ichizo; Ishizu, Akihiro

Phorbol 12-myristate 13-acetate stimulation under hypoxia induces nuclear swelling with DNA outflow but not extracellular trap formation of neutrophils

Masuda, Sakiko; Kato, Kurumi; Ishibashi, Misato et al.

Experimental and Molecular Pathology, 2022, 125, 104754

Permalink : https://hdl.handle.net/2115/84658

このアイテムのアクセス数:547件（2026-10-14 02:23 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/84658
タイトル	Phorbol 12-myristate 13-acetate stimulation under hypoxia induces nuclear swelling with DNA outflow but not extracellular trap formation of neutrophils
著者	Masuda, Sakiko ; Kato, Kurumi ; Ishibashi, Misato ; Nishibata, Yuka ; Sugimoto, Ayako ; Nakazawa, Daigo ; Tanaka, Satoshi ; Tomaru, Utano ; Tsujino, Ichizo ; Ishizu, Akihiro
e-Rad_Researcher 10763617 著者名 Masuda, Sakiko
著者名 Kato, Kurumi
著者名 Ishibashi, Misato
著者名 Nishibata, Yuka
著者名 Sugimoto, Ayako
e-Rad_Researcher 60724135 著者名 Nakazawa, Daigo
e-Rad_Researcher 30374250 著者名 Tanaka, Satoshi
e-Rad_Researcher 20360901 著者名 Tomaru, Utano
e-Rad_Researcher 00344507 著者名 Tsujino, Ichizo
e-Rad_Researcher 60321957 著者名 Ishizu, Akihiro
言語	英語
キーワード	Neutrophil extracellular traps
	Hypoxia
	DNase I
	Actin
発行日	2022-04
出版者	Elsevier
収録物名	Experimental and Molecular Pathology
巻(号)	125
ページ	104754
抄録	Neutrophils stand sentinel over infection and possess diverse antimicrobial weapons, including neutrophil extracellular traps (NETs). NETs are composed of web-like extracellular DNA decorated with antimicrobial substances and can trap and eliminate invading microorganisms. Although phorbol 12-myristate 13-acetate (PMA) is a potent NET inducer, previous studies have demonstrated that not all neutrophils exhibit NET formation even if stimulated by PMA at high concentrations. This study first showed that some neutrophils stimulated by PMA displayed a swollen nucleus but not NET formation and that hypoxic environments suppressed the NET release. Next, characterization of PMA-stimulated neutrophils with a swollen nucleus was accomplished by differentiating between suicidal-type NETosis and apoptosis. Furthermore, the significance of the phenomenon was examined using formalin-fixed, paraffin-embedded human lung disease tissues with and without pneumonia. As a result, histone H3 citrullination, DNA outflow, propidium iodide labeling, resistance to DNase I, and suspended actin rearrangement were characteristics of PMA-stimulated neutrophils with a swollen nucleus distinct from neutrophils that underwent either suicidal-type NETosis or apoptosis. Neutrophils stimulated by PMA under hypoxic conditions secreted matrix metalloproteinase-9 cytotoxic to human lung-derived fibroblasts. Further, deposition of neutrophil-derived citrullinated histone H3+ chromatin substances in pulmonary lesions was greater in patients with pneumonia than in patients without pneumonia and positively correlated with hypoxia-inducible factor-1α expression. The collective findings suggested that neutrophils activated under hypoxic conditions could be putative modulators of hypoxia-related disease manifestations.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
PISSN	0014-4800
EISSN	1096-0945
関連情報	PMID 35259405
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1016/j.yexmp.2022.104754