Phagocyte NADPH oxidase: a multicomponent enzyme essential for host defenses.
Phagocytes such as neutrophils and monocytes play an essential role in host defenses against microbial pathogens. Reactive oxygen species (ROS), such as superoxide anion, hydrogen peroxide, the hydroxyl radical, and hypochlorous acid, together with microbicidal peptides and proteases, constitute their antimicrobial arsenal. The enzyme responsible for superoxide anion production and, consequently, ROS generation, is called NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of cytosolic proteins (p47phox, p67phox, p40phox, and rac1/2) and membrane proteins (p22phox and gp91phox, which form cytochrome b558) which assemble at membrane sites upon cell activation. The importance of this enzyme in host defenses is illustrated by a life-threatening genetic disorder called chronic granulomatous disease in which the phagocyte enzyme is dysfunctional, leading to life-threatening bacterial and fungal infections. Also, because ROS can damage surrounding tissues, their production, and thus NADPH oxidase activation, must be tightly regulated. This review describes the structure and activation of the neutrophil NADPH enzyme complex.
El-Benna
Jamel
J
Unité Inserm U479, Centre Hospitalo-Universitaire Xavier Bichat, Paris, France. benna@bichat.inserm.fr
Dang
Pham My-Chan
PM
Gougerot-Pocidalo
Marie-Anne
MA
Elbim
Carole
C
D000818:Animals; D000838:Anions; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D006105:Granulomatous Disease, Chronic / Q000473:pathology; D006801:Humans; D007107:Immune System / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology*; D010586:Phagocytes / Q000201:enzymology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides
D000838:Anions; D017382:Reactive Oxygen Species; D013481:Superoxides; D019255:NADPH Oxidases