Winrow V R, Winyard P G, Morris C J, Blake D R
ARC Bone and Joint Research Unit, London Hospital Medical College.
Br Med Bull. 1993 Jul;49(3):506-22. doi: 10.1093/oxfordjournals.bmb.a072627.
In recent years it has become increasingly apparent that, in man, free radicals play a role in a variety of normal regulatory systems, the deregulation of which may play an important role in inflammation. As examples, we discuss the second messenger roles of: NO in the regulation of vascular tone, O2.- in fibroblast proliferation and H2O2 in the activation of transcription factors such as NF kappa B. Other control mechanisms, the physiological function of which may be perturbed in inflammation, include: the oxidative modification of low density lipoprotein, the oxidative inactivation of alpha-1-protease inhibitor, DNA damage/repair and heat shock protein synthesis. At sites of inflammation, increased free radical activity is associated with the activation of the neutrophil NADPH oxidase and/or the uncoupling of a variety of redox systems, including endothelial cell xanthine dehydrogenase. Although free radicals, thus produced, have the capacity to mediate tissue destruction, either alone or in concert with proteases, we argue that disturbances in the second messenger and regulatory activities of free radicals may also contribute significantly to the inflammatory process.
近年来越来越明显的是，在人类中，自由基在多种正常调节系统中发挥作用，这些系统的失调可能在炎症中起重要作用。作为例子，我们讨论以下物质的第二信使作用：一氧化氮在血管张力调节中的作用、超氧阴离子在成纤维细胞增殖中的作用以及过氧化氢在激活转录因子如核因子κB中的作用。其他控制机制，其生理功能在炎症中可能受到干扰，包括：低密度脂蛋白的氧化修饰、α-1-蛋白酶抑制剂的氧化失活、DNA损伤/修复和热休克蛋白合成。在炎症部位，自由基活性增加与中性粒细胞NADPH氧化酶的激活和/或包括内皮细胞黄嘌呤脱氢酶在内的多种氧化还原系统的解偶联有关。尽管如此产生的自由基有能力单独或与蛋白酶协同介导组织破坏，但我们认为自由基的第二信使和调节活性的紊乱也可能对炎症过程有显著贡献。
