harmful waste products as novel immune modulators for treating inflammatory arthritis有害废物作为新型的免疫调节剂治疗类风湿性关节炎.pdfVIP

Perspectives Harmful Waste Products as Novel Immune Modulators for Treating Infl ammatory Arthritis? Andrew P. Cope The Role of Reactive Oxygen Species For many years, reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and hydroxyl radicals, and their reaction products, were classically described as harmful by-products of aerobic metabolism capable of causing DNA mutations, lipid peroxidation, and protein oxidation [1]. The identifi cation of enzymes such as superoxide dismutase, catalase, and peroxidase that served to eliminate these waste products rather substantiated this view. It soon became clear, however, that there existed a family of enzymes whose function it was to deliberately generate ROS. The fi rst of these was NADPH oxidase, which is responsible for the respiratory burst in neutrophils and macrophages in response to microbes or infl ammatory cytokines [2]. The DOI: 10.1371/journal.pmed.0030385.g001 catalytic centre of NADPH oxidase is the membrane-associated protein Figure 1. Structure and Function of the NADPH Oxidase Complex gp91phox (see Glossary) complexed with Schematic of the molecular composition of the NADPH oxidase complex. The principal subunits are shown, together with some of the key cellular and molecular modifi cations that arise following phox p22 . Activation requires association activation of stress pathways and the generation of superoxide (O2−). Two molecules of superoxide with a phosphorylated form of p47phox can react to generate hydrogen peroxide (H O ). In the presence of iron, superoxide and H O 2 2 2 2 phox react to generate hydroxyl