Mechanisms for the activation/electron transfer of neutrophil NADPH-oxidase complex and molecular pathology of chronic granulomatous disease.

Professional phagocytes, neutrophils, possess a unique membrane-associated NADPH-oxidase system, dormant in resting cells, which becomes activated upon exposure to the appropriate stimuli and catalyzes the one-electron reduction of molecular oxygen to superoxide, O2-. Oxidase activation involves the assembly, in the plasma membrane, of membrane-bound and cytosolic constituents of the oxidase system, which are disassembled in the resting state. The oxidase system consists of two plasma membrane-bound components; low-potential cytochrome b558, which is composed of two subunits of 22-kDa, and 91-kDa, and a possible flavoprotein related to the electron transport between NADPH and cytochrome b558. Recent reports have indicated that FAD-binding sites of the oxidase are contained in cytochrome b558. At least two cytosolic components, 67-kDa protein and a phosphorylated 47-kDa protein, are known to translocate to the plasma membrane, ensuring assembly of an active O2(-)-generating NADPH-oxidase system. It is the purpose of this review to focus on recent data concerning electron transfer mechanisms of the activated neutrophil NADPH-oxidase complex and molecular pathology of chronic granulomatous disease.