The superoxide‐generating oxidase of phagocytic cells

Abstract

Professional phagocytes (neutrophils, eosinophils, monocytes and macrophages) possess an enzymatic complex, the NADPH oxidase, which is able to catalyze the one‐electron reduction of molecular oxygen to superoxide, O 2 − . The NADPH oxidase is dormant in non‐activated phagocytes. It is suddenly activated upon exposure of phagocytes to the appropriate stimuli and ther by contributes to the microbicidal activity of these cells. Oxidase activation in phagocytes involves the assembly, in the plasma membrane, of membrane‐bound and cytosolic components in phagocytes involves the assembly, in the plasma membrane, of membrane‐bound and cytosolic components of the oxidase complex, which were disassembled in the resting state. One of the membrane‐bound components in resting phagocytes has been identified as a low‐potential b ‐type cytochrome, a heterordimer composed of two subunits of 22‐kDa. The link between NADPH and cytochrome b is probably a flavoprotein whose subcellular localizaion in resting phagocytes remains to be determined. Genetic defects in the cytochrome b subunits and in the cytosolic factors have been shown to be the molecular basis of chronic granulomatous disease, a group of inherited disorders in the host defense, characterized by severe, recurrent bacterial and fungal infections in which phagocytic cells fail generate O 2 − upon stimulation. The present review is focused on recent data concerning the singnaling pathway which leads to oxidase activation, including specific receptors, the producion of second messengers, the organization of the oxidase complex and the molecular defects responsible for granulomatous disease.