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Formation of neutrophil extracellular traps in mitochondrial DNA-deficient cells.
Takishita, Yutaka; Yasuda, Hiroyuki; Shimizu, Mio; Matsuo, Akane; Morita, Akihiro; Tsutsumi, Tomonari; Tsuchiya, Masahiko; Sato, Eisuke F.
  • Takishita Y; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka-city, Mie 513-8670, Japan.
  • Yasuda H; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka-city, Mie 513-8670, Japan.
  • Shimizu M; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka-city, Mie 513-8670, Japan.
  • Matsuo A; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka-city, Mie 513-8670, Japan.
  • Morita A; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka-city, Mie 513-8670, Japan.
  • Tsutsumi T; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka-city, Mie 513-8670, Japan.
  • Tsuchiya M; Department of Anesthesiology, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno, Osaka 545-8586, Japan.
  • Sato EF; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka-city, Mie 513-8670, Japan.
J Clin Biochem Nutr ; 66(1): 15-23, 2020 Jan.
Article en En | MEDLINE | ID: mdl-32001952
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 (ρ0 cells) by treating HL-60 cells with dideoxycytidine and differentiated them to neutrophil-like cells. These neutrophil-like ρ0 cells showed markedly reduced NOX-independent NET formation but not NOX-dependent NET formation. However, NET-associated intracellular histone citrullination was not inhibited in ρ0 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.
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