Opening the black box: lessons from cell-free systems on the phagocyte NADPH-oxidase.
The NADPH-oxidase complex of phagocytic cells plays a key role in the defense against invading pathogens, through the release of superoxide anion, precursor of other reactive oxygen species (ROS). NADPH-oxidase deficiency is called Chronic Granulomatous Disease (CGD), in which patients suffer from recurrent infections and from the formation of granulomas in various organs. Research on NADPH-oxidase has much benefited from the discovery of cell-free systems, i.e. reconstitution assays from broken resting (unstimulated) phagocytes, in which activation of the oxidase is elicited in vitro. Cell-free systems were developed in parallel to studies of molecular defects of patients with CGD, both approaches leading to the identification of the major proteins implicated in enzyme activation. Variations around the cell-free system allowed molecular dissection of the mechanism of NADPH-oxidase activation and provided insights into its relationship to phagocytosis.
Dagher
Marie-Claire
MC
Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, F-38027 Grenoble; CEA;CNRS; Université Joseph Fourier; France. marie-claire.dagher@ibs.fr
Pick
Edgar
E
D000818:Animals; D002474:Cell-Free System / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism*; D010586:Phagocytes / Q000201:enzymology* / Q000378:metabolism; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D019255:NADPH Oxidases