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.

中文翻译：

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NADPH氧化酶调节中性粒细胞胞外陷阱的Ca 2+依赖性形成。

摘要-

慢性肉芽肿病（CGD）是一种严重的遗传性免疫缺陷，与细菌和真菌的反复感染以及异常的炎症过程有关。CGD表型取决于吞噬NADPH氧化酶的缺乏，导致吞噬细胞无法产生活性氧（ROS）。这样的吞噬细胞执行吞噬作用，脱粒和形成嗜中性粒细胞外陷阱（NETs）的能力有限，这是对许多受体和药理刺激的反应。然而，作者的一项研究先前已经描述了响应钙离子载体而使CGD患者中性粒细胞捕获。一些研究表明，NADPH-氧化酶缺陷型中性粒细胞不仅不能产生ROS，而且对细胞外Ca的流入具有重大干扰。^{2 +是} 由于在激活过程中缺乏酶的生电功能和膜去极化，因此在促炎细胞因子合成中存在多种异常。在这项研究中，已经表明由钙离子载体A23187响应的NADPH氧化酶缺陷中性粒细胞形成NETs伴随着细胞内Ca ^2+的过度积累。我们提出这种违反是由于突变体NADPH氧化酶中通常没有诱导质膜去极化的电功能的缘故。结果表明吞噬NADPH氧化酶作为细胞外Ca ²⁺转运的调节剂具有重要作用，可用于寻找CGD的治疗方法。