NADPH Oxidase Modulates Ca 2+ -Dependent Formation of Neutrophil Extracellular Traps
- PDF / 530,649 Bytes
- 6 Pages / 612 x 792 pts (letter) Page_size
- 55 Downloads / 186 Views
ARCH ARTICLE
NADPH Oxidase Modulates Ca2+-Dependent Formation of Neutrophil Extracellular Traps N. V. Vorobjevaa,* and B. V. Chernyakb a Department b Belozersky
of Immunology, Faculty of Biology, Moscow State University, Moscow, 119991 Russia Scientific Research Institute of Physical and Chemical Biology, Moscow State University, Moscow, 119992 Russia *e-mail: [email protected] Received April 30, 2020; revised June 3, 2020; accepted June 23, 2020
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. Keywords: human neutrophils, oxidative burst, reactive oxygen species, neutrophil extracellular traps, NETosis, chronic granulomatous disease DOI: 10.3103/S0096392520030104
INTRODUCTION Chronic granulomatous disease (CGD) is an inherited immunodeficiency characterized by the inability of phagocytes to produce superoxide anion radicals (O–2 ) and their derivatives [1]. The abortive generation of superoxide anion radicals is associated with the deficiency of the multicomponent enzyme complex NADPH oxidase [2], occurring due to the mutations in genes encoding its subunits (p47phox, p67phox, p40phox, gp91phox, p22phox, and Rac2 GTPase). CGD patients suffer from recurrent bacterial and fungal infections as well as aberrant inflammatory processes. Therefore, the understanding of the signaling pathways responsible for the CGD phenotype is important for finding the treatment approaches to this disease. It has previously been shown that the stimulation of neutrophils by receptor stimuli is accompanied by
Data Loading...
