Abstract—
Chronic granulomatous disease (CGD) is a severe hereditary immunodeficiency associated with recurrent bacterial and fungal infections as well as aberrant inflammatory processes. The CGD phenotype depends on the deficiency of phagocytic NADPH oxidase causing the inability of phagocytes to produce reactive oxygen species (ROS). Such phagocytes have a limited ability to execute phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs) as a reaction to many receptor and pharmacological stimuli. However, neutrophil trapping in CGD patients in response to calcium ionophores has been previously described in one of the authors' studies. Some researches have shown that NADPH-oxidase-deficient neutrophils are not only incapable of generating ROS but also have major disturbances in the influx of extracellular Ca2+ due to the absence of the electrogenic function of the enzyme and the membrane depolarization during the activation and consequently multiple abnormalities in the synthesis of proinflammatory cytokines. In this study, it has been shown that the formation of NETs by neutrophils deficient in NADPH oxidase in response to calcium ionophore A23187 is accompanied by excessive accumulation of intracellular Ca2+. We propose that this violation is because of the absence of the electrogenic function in mutant NADPH oxidase that normally induces depolarization of the plasma membrane. The results have indicated the important role of phagocytic NADPH oxidase as a modulator of extracellular Ca2+ transport and that it can be used to find the cure for CGD.
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This study was supported by the Russian Foundation for Basic Research (project no. 17–00–00088).
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Statement of compliance with standards of research involving humans as subjects. Informed consent was obtained from all individual participants involved in the study. The research was conducted according to the Helsinki Declaration on the Ethical Principles for Medical Research (2000) and the European Council Convention Protocol on Human Rights and Biomedicine (1999). The study was approved by the local committee on ethics of the Russian Children’s Clinical Hospital of the Pirogov Russian National Research Medical University of the Ministry of Health of Russia.
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Translated by E. Sherstyuk
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Vorobjeva, N.V., Chernyak, B.V. NADPH Oxidase Modulates Ca2+-Dependent Formation of Neutrophil Extracellular Traps. Moscow Univ. Biol.Sci. Bull. 75, 104–109 (2020). https://doi.org/10.3103/S0096392520030104
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DOI: https://doi.org/10.3103/S0096392520030104