title: Effects of the antioxidants Trolox, Tiron and Tempol on neutrophil extracellular trap formation.
abstract: Neutrophils can entrap and kill pathogens by releasing of neutrophil extracellular traps (NETs), in addition to their routine functions such as phagocytosis and degranulation. NETs consist of a DNA backbone supplemented by multiple bactericidal proteins from the nucleus, the cytoplasm and the granules. Neutrophils release NETs after their activation by a number of physiological and pharmacological stimuli. In addition to the antimicrobial function, NETs are involved in the pathogenesis of various autoimmune and inflammatory diseases. Since NET formation predominantly depends on the generation of reactive oxygen species (ROS), all substances that are capable of scavenging ROS or inhibiting the enzymes responsible for their synthesis should prevent ROS-associated NET release. The aim of this study was to test substances with an antioxidant activity, such as Trolox, Tiron, and Tempol, for their capacity to inhibit NET formation by primary human neutrophils in vitro. We revealed for the first time an inhibitory effect of Trolox on ROS-dependent NET release. We also established a suppressive effect of Tempol on NET formation that manifested itself in a wide range of concentrations. In this study, no inhibitory influence of Tiron on NET release was revealed. All tested substances exerted a significant dose-dependent antioxidative effect on ROS generation induced by phorbol 12-myristate 13-acetate (PMA). We suggest that the antioxidants Trolox and Tempol should be recommended for treating autoimmune and inflammatory diseases that implicate ROS-dependent NET release.
authors.affiliation: Biology Faculty, Lomonosov Moscow State University, Lenin Hills 1/12, 119991 Moscow, Russia. Electronic address: nvvorobjeva@mail.ru.
authors.forename: Nina V
authors.initials: NV
authors.lastname: Vorobjeva
authors.affiliation: Institute of Immunology, Federal Medical Biological Agency, Kashirskoe Shosse 24/2, 115478 Moscow, Russia. Electronic address: bvpinegin@mail.ru.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Pinegin
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D065206:Extracellular Traps / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013113:Spin Labels; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002839:Chromans; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D013755:Tetradecanoylphorbol Acetate; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C001803:tempol
keywords: NETosis; NETs; Neutrophil extracellular traps; Neutrophils; Reactive oxygen species