ROI production by the neutrophil.(A) The resting neutrophil has several classes of specialized lysosomal granules containing myeloperoxidase (MPO) together with about a dozen types of antimicrobial polypeptides (AMP). The membrane of the granules bears two chains of the phagocyte oxidase (phox) complex, phox91 and phox22. The cytosol contains three more components: phox47, phox67, and phox40; a sixth component, the GTPase Rac, lies at the plasma membrane.(B) When the neutrophil is activated—for example, upon encounter with a microbial pathogen—its granules fuse with the cell membrane, discharging MPO and AMP into the forming phagosome or extracellular space. The six components of phox unite at the plasma membrane and transfer electrons from reduced nicotinamide adenine dinucleotide phosphate (NADPH) in the cytosol to O2 in the extracytosolic space, forming superoxide (· O2−).· O2− dismutates to hydrogen peroxide (H2O2), which interacts with· O2− to form hydroxyl radical (· OH). MPO catalyzes the H2O2-dependent oxidation of ambient halides to hypohalites.(C) Wentworth et al.(3) propose additional reactions catalyzed by antibody (Y-shape). Antibody is either free in the extracellular fluid, or attached nonspecifically to the neutrophil, or attached specifically to the microbial pathogen. Phox produces singlet oxygen (1O2*), perhaps indirectly by way of MPO. Antibody catalyzes the conversion of 1O2* to H2O2 and the reactive species ozone (O3). H2O2+ O3 can react to produce the· OH radical.(Not all reactants and products are shown, and stoichiometry is not indicated.)