Dagher Marie-Claire, Pick Edgar
Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, F-38027 Grenoble; CEA;CNRS; Université Joseph Fourier; France.
Biochimie. 2007 Sep;89(9):1123-32. doi: 10.1016/j.biochi.2007.03.002. Epub 2007 Mar 12.
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.
吞噬细胞的NADPH氧化酶复合物在抵御入侵病原体方面发挥着关键作用，它通过释放超氧阴离子（其他活性氧物质的前体）来实现这一功能。NADPH氧化酶缺乏症被称为慢性肉芽肿病（CGD），患有这种疾病的患者会反复感染，并在各个器官形成肉芽肿。对NADPH氧化酶的研究得益于无细胞系统的发现，即从破碎的静息（未受刺激）吞噬细胞中进行重组分析，在体外引发氧化酶的激活。无细胞系统是与对CGD患者分子缺陷的研究并行开发的，这两种方法都导致了参与酶激活的主要蛋白质的鉴定。围绕无细胞系统的各种变体使得对NADPH氧化酶激活机制进行分子剖析，并深入了解其与吞噬作用的关系。
