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线粒体DNA缺陷细胞中中性粒细胞胞外陷阱的形成。

Formation of neutrophil extracellular traps in mitochondrial DNA-deficient cells.

作者信息

Takishita Yutaka, Yasuda Hiroyuki, Shimizu Mio, Matsuo Akane, Morita Akihiro, Tsutsumi Tomonari, Tsuchiya Masahiko, Sato Eisuke F

机构信息

Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka-city, Mie 513-8670, Japan.

Department of Anesthesiology, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno, Osaka 545-8586, Japan.

出版信息

J Clin Biochem Nutr. 2020 Jan;66(1):15-23. doi: 10.3164/jcbn.19-77. Epub 2019 Nov 12.

DOI:10.3164/jcbn.19-77
PMID:32001952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6983440/
Abstract

Neutrophil extracellular trap (NET) formation plays an important role in inflammatory diseases. Although it is known that NET formation occurs via NADPH oxidase (NOX)-dependent and NOX-independent pathways, the detailed mechanism remains unknown. Therefore, in this study, we aimed to elucidate the role of mitochondria in NOX-dependent and NOX-independent NET formation. We generated mitochondrial DNA-deficient cells (ρ cells) by treating HL-60 cells with dideoxycytidine and differentiated them to neutrophil-like cells. These neutrophil-like ρ cells showed markedly reduced NOX-independent NET formation but not NOX-dependent NET formation. However, NET-associated intracellular histone citrullination was not inhibited in ρ cells. Furthermore, cells membrane disruption in NOX-dependent NET formation occurred in a Myeloperoxidase (MPO) and mixed lineage kinase domain like pseudokinase (MLKL)-dependent manner; however, cell membrane disruption in NOX-independent NET formation partially occurred in an MLKL-dependent manner. These results highlight the importance of mitochondria in NOX-independent NET formation.

摘要

中性粒细胞胞外诱捕网（NET）的形成在炎症性疾病中起重要作用。虽然已知NET的形成通过NADPH氧化酶（NOX）依赖性和非NOX依赖性途径发生，但其详细机制仍不清楚。因此，在本研究中，我们旨在阐明线粒体在NOX依赖性和非NOX依赖性NET形成中的作用。我们通过用双脱氧胞苷处理HL-60细胞来生成线粒体DNA缺陷细胞（ρ细胞），并将它们分化为中性粒细胞样细胞。这些中性粒细胞样ρ细胞显示非NOX依赖性NET形成明显减少，但NOX依赖性NET形成未受影响。然而，NET相关的细胞内组蛋白瓜氨酸化在ρ细胞中未被抑制。此外，NOX依赖性NET形成中的细胞膜破坏以髓过氧化物酶（MPO）和混合谱系激酶结构域样假激酶（MLKL）依赖性方式发生；然而，非NOX依赖性NET形成中的细胞膜破坏部分以MLKL依赖性方式发生。这些结果突出了线粒体在非NOX依赖性NET形成中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/850912caf695/jcbn19-77f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/4678c566dd5d/jcbn19-77f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/42868e4c1150/jcbn19-77f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/35c4a679ee25/jcbn19-77f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/d44d50750a71/jcbn19-77f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/4675f6073149/jcbn19-77f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/6217193d3919/jcbn19-77f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/850912caf695/jcbn19-77f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/4678c566dd5d/jcbn19-77f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/42868e4c1150/jcbn19-77f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/35c4a679ee25/jcbn19-77f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/d44d50750a71/jcbn19-77f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/4675f6073149/jcbn19-77f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/6217193d3919/jcbn19-77f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5de8/6983440/850912caf695/jcbn19-77f07.jpg

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