title: Singlet oxygen is essential for neutrophil extracellular trap formation.
abstract: Neutrophil extracellular traps (NETs) that bind invading microbes are pivotal for innate host defense. There is a growing body of evidence for the significance of NETs in the pathogenesis of infectious and inflammatory diseases, but the mechanism of NET formation remains unclear. Previous observation in neutrophils of chronic granulomatous disease (CGD) patients, which defect NADPH oxidase (Nox) and fail to produce reactive oxygen species (ROS), revealed that ROS contributed to the formation of NETs. However, the active species were not identified. In this study, we discovered that singlet oxygen, one of the ROS, mediated Nox-dependent NET formation upon stimulation with phorbol myristate acetate. We also revealed that singlet oxygen itself could induce NET formation by a distinct system generating singlet oxygen with porfimer sodium (Photofrin) in CGD neutrophils, as well as healthy neutrophils. This was independent of Nox activation. These results show that singlet oxygen is essential for NET formation, and provide novel insights into the pathogenesis of infectious and inflammatory diseases.
authors.affiliation: School of Human Health Science, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nishinaka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Arai
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
authors.forename: Kouhei
authors.initials: K
authors.lastname: Yamashita
mesh_terms: D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D017323:Dihematoporphyrin Ether / Q000378:metabolism / Q000494:pharmacology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology; D006105:Granulomatous Disease, Chronic / Q000276:immunology; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D026082:Singlet Oxygen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D026082:Singlet Oxygen; D017323:Dihematoporphyrin Ether; D013755:Tetradecanoylphorbol Acetate; D000077553:Edaravone; D000983:Antipyrine