Аннотация:Introduction. At the sites of infection, neutrophil protective weapons are activated, in particular phagocytosis, oxidative burst, exocytosis of various granule types, and release of DNA-based extracellular traps (NETosis). The initiation of NETosis after recognition of pathogens by specific receptors is mediated by increase in intracellular Ca2+ concentration, therefore, the use of Ca2+ ionophore A23187 can be considered as semi-physiological model of NETosis. Induction of NETosis by various stimuli depends on reactive oxygen species (ROS) produced by enzymatic complex NADPH oxidase, however NETosis induced by Ca2+ ionophores was suggested to be mediated by ROS produced in mitochondria (mtROS) or without any ROS in general.Materials and methods. A wide inhibitor analysis has been used as well as luminol-amplified chemiluminescence assay and fluorescence detection of neutrophil extracellular traps.Results and discussion. Using mitochondria-targeted antioxidant SkQ1 and specific inhibitors of NADPH oxidase, we showed that both sources of ROS, mitochondria and NADPH oxidase, are involved in NETosis induced by A23187 in human neutrophils. In support of critical role of mtROS, SkQ1-sensitive NETosis was demonstrated to be induced by A23187 in neutrophils from patients with chronic granulomatous disease (CGD). We assume that Ca2+-triggered mtROS production contributes to NETosis either directly (CGD neutrophils) or by stimulating NADPH oxidase. The opening of the mitochondrial permeability transition pore (mPTP) in neutrophils treated by A23187 was revealed using electron transmission microscopy as a swelling of mitochondrial matrix. Using specific inhibitors, we demonstrated that mPTP is involved in mtROS production, NETosis, and the oxidative burst induced by A23187.