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

Formation of neutrophil extracellular traps in mitochondrial DNA-deficient cells. J Clin Biochem Nutr. 2020 Jan;66(1):15-23 Authors: Takishita Y, Yasuda H, Shimizu M, Matsuo A, Morita A, Tsutsumi T, Tsuchiya M, Sato EF 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. PMID: 32001952 [PubMed]
Source: Journal of Clinical Biochemistry and Nutrition - Category: Nutrition Tags: J Clin Biochem Nutr Source Type: research