The superoxide-generating oxidase of phagocytic cells. Physiological, molecular and pathological aspects.
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, O2-. The NADPH oxidase is dormant in non-activated phagocytes. It is suddenly activated upon exposure of phagocytes to the appropriate stimuli and thereby 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 of the oxidase complex, which were diassembled in the resting state. One of the membrane-bound components in resting phagocytes has been identified as a low-potential b-type cytochrome, a heterodimer composed of two subunits of 22-kDa and 91-kDa. The link between NADPH and cytochrome b is probably a flavoprotein whose subcellular localization 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 to generate O2- upon stimulation. The present review is focused on recent data concerning the signaling pathway which leads to oxidase activation, including specific receptors, the production of second messengers, the organization of the oxidase complex and the molecular defects responsible for granulomatous disease.
Morel
F
F
Département de Biologie Moléculaire et Structurale, Centre d'Etudes Nucléaires, Grenoble, France.
Doussiere
J
J
Vignais
P V
PV
D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D006105:Granulomatous Disease, Chronic / Q000235:genetics; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000502:physiology*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology*; D016897:Respiratory Burst / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme