The superoxide-forming enzymatic system of phagocytes

The formation of oxygen-derived free radicals by the phagocytes (neutrophils, eosinophils, monocytes and macrophages) is catalysed by a membrane-bound NADPH oxidase which is dormant in resting cells and becomes activated during phagocytosis or following interaction of the cells with suitable soluble stimulants. This enzyme is under investigation in many laboratories but its molecular structure remains to be clarified. Possible components such as flavoproteins, cytochrome b558, and quinones have been proposed on the basis of enzyme purification studies, effects of inhibitors, kinetic properties and analysis of genetic defects of the oxidase. An extensive discussion of the evidence for the participation of these constituents is reported. On the basis of the available information on the structure and the catalytic properties of the NADPH oxidase, a series of possible models of the electron-transport chain from NADPH to O2 is presented. Finally, the triggering mechanism of the respiratory burst is discussed, with particular reference to the stimulus-response coupling and the final modification(s) of the oxidase (phosphorylation, assembly, change of lipid environment, etc.) which are involved in its activation.