NOX2 generates superoxide anion from oxygen

Phagocytic cells kill microorganisms by ingesting them into phagocytic vacuoles (phagosomes). Phagocytosis is accompanied by the activation of the NADPH oxidase (NOX2 complex), a multiprotein enzyme complex, that assembles in the phagosomal membrane (Winterbourn C et al. 2006). The NOX2 complex shuttles electrons from NADPH in the cytoplasm across the membrane to oxygen in the phagosomal lumen converting oxygen into the superoxide radical anion (O2.-). As this electron transfer creates a charge imbalance that would otherwise depolarize the membrane, NADPH oxidase activity is accompanied by activation of the V-ATPase and voltage-gated proton channel (Demaurex N & El Chemaly A 2010; El Chemaly A et al. 2010; Nunes P et al. 2013).<p>Defects in NADPH oxidase components are associated with chronic granulomatous disease (CGD) (de Oliveira-Junior EB et al. 2011). Phagocytic cells of CGD patients are unable to produce superoxide ion, and their efficiency in bacterial killing is significantly impaired (Johnston RB Jr et al. 1975; de Oliveira-Junior EB et al. 2011). In addition, macrophages from CGD patients exhibit abnormal function because these cells release higher levels of anti-inflammatory cytokines and lower levels of proinflammatory cytokines in response to bacterial stimuli (Rahman FZ et al. 2009).

吞噬细胞通过将微生物摄入吞噬泡（即噬体）中而将其消灭。吞噬作用伴随着NADPH氧化酶（NOX2复合物）的激活，该复合物是一种多蛋白酶复合物，在噬体膜（Winterbourn C 等人，2006年）上组装。NOX2复合物将细胞质中的NADPH电子跨膜传递至噬体腔内的氧气，将氧气转化为超氧阴离子（O2-）。由于这种电子转移产生了可能导致膜去极化的电荷不平衡，因此NADPH氧化酶的活性伴随着V-ATPase和电压门控质子通道的激活（Demaurex N & El Chemaly A，2010年；El Chemaly A 等人，2010年；Nunes P 等人，2013年）。NADPH氧化酶成分的缺陷与慢性肉芽肿病（CGD）相关（de Oliveira-Junior EB 等人，2011年）。CGD患者的吞噬细胞无法产生超氧离子，其细菌杀伤效率显著降低（Johnston RB Jr 等人，1975年；de Oliveira-Junior EB 等人，2011年）。此外，CGD患者的巨噬细胞表现出异常功能，因为这些细胞对细菌刺激的反应是释放更高水平的抗炎细胞因子和更低水平的促炎细胞因子（Rahman FZ 等人，2009年）。