NADPH oxidase modulates Ca2+-dependent formation of neutrophil extracellular traps
Abstract
Chronic granulomatous disease (CGD) is a severe inherited immunodeficiency characterized by recurrent bacterial and fungal infections and aberrant inflammation. The CGD phenotype is due to deficiency of phagocytic NADPH oxidase, unable to generate reactive oxygen species (ROS). Such phagocytes are limited in phagocytosis and degranulation as well as a unique means of combating pathogens, neutrophil extracellular traps (NETs) formation, in response to many receptor and pharmacological stimuli. However, activation of NET formation by neutrophils isolated from the blood of CGD patients in response to calcium ionophores was described in our recent study. As was shown previously, neutrophils deficient in NADPH oxidase are not only unable to form ROS, but also have deficiency in the electrogenic activity of the enzyme and membrane depolarization upon activation. Therefore, these neutrophils have impaired extracellular Ca2+ influx and, as a result, multiple disorders in the synthesis of proinflammatory cytokines. In the present study, we showed that NET formation by CGD neutrophils in response to calcium ionophore A23187 is accompanied by excessive accumulation of intracellular Ca2+. We explain this disorder by the deficiency of the electrogenic function of mutant NADPH oxidase, which in healthy donor neutrophils causes membrane potential depolarization. The results obtained in our study indicate an important function of phagocytic NADPH oxidase as a modulator of Ca2+-dependent signaling pathways, and potentially can be used for treatment of CGD.
About the Authors
N. V. Vorobjeva
Lomonosov Moscow State University
Russian Federation
Russian Federation
Leninskiye gory 1–12, Moscow, 119234
B. V. Chernyak
A.N. Belozersky Institute of Physico-Chemical Biology; Lomonosov Moscow State University
Russian Federation
Leninskiye gory 1–40, Moscow, 119992
Russian Federation
Leninskiye gory 1–40, Moscow, 119992
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Review
For citations:
Vorobjeva N.V., Chernyak B.V. NADPH oxidase modulates Ca2+-dependent formation of neutrophil extracellular traps. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2020;75(3):131-137. (In Russ.)
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