Role of granules and reactive oxygen species in phagosome formation and function. (A): Granules deliver phagocytic machinery to the plasma and phagosome membranes during phagocytosis. Secretory vesicles supply phagocytic receptors to the plasma membrane. Specific and gelatinase granules deliver NADPH oxidase components and ion channels to the phagosome membrane. Azurophil granules supply myeloperoxidase (MPO) and cytotoxic proteins and proteases, including elastase. (B) Reactive oxygen species (ROS) and granules contribute synergistically to microbial killing. NADPH oxidase translocates electrons into the phagosome which react with molecular oxygen to form superoxide (O2.−). Electrogenic charge is compensated by proton (H+) influx, predominantly through Hv1 channels. MPO catalyzes the reaction of O2.− and H+ to form hydrogen peroxide (H2O2). Chloride (Cl−) enters the phagosome, for example, through CFTR channels. MPO oxidizes Cl− to form HOCl which is likely to be directly microbicidal. Non‐oxidative proteins and proteases, for example, elastase and cathepsin G, are also directly microbicidal. Numbers in blue indicate clinical syndromes associated with mutations in various steps of the pathway (Table 1)