Meta-Biol

• Pathways

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).

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).