In Vivo Detection of Free Radical Generation

我们已经设定了研究重点，将重点放在疾病和毒性的动物模型中自由基的产生，这些动物模型有很强的环境因素。环境因素增加疾病风险和毒性的方式仍然知之甚少。在过去，我们的工作主要集中在有毒金属和有机化合物中自由基的体内形成和检测，并扩展到内毒素本身引起的炎症过程中的自由基形成的研究，以及与柴油车尾气颗粒物的结合。现在继续进行环境外毒素和病原体的研究，目的是了解与特殊器官感染、免疫性疾病和肥胖症有关的基本自由基机制。 体内自旋捕获技术是目前检测体内高活性自由基分子最成功的方法。该小组继续使用自旋捕获来解决体外生化和体内毒理学疾病问题，使用两种主要的自旋捕获方法，即ESR检测或抗体识别和MS鉴定被捕获的自由基。 通过使用体内自旋捕获方法，这些研究检验了以下假设：1)自由基在肺部感染、肥胖和过敏反应的复杂发病机制中是致病分子；2)特定的生物化学途径参与触发自由基的产生，这些自由基可能作为与人类免疫和疾病反应相关的炎症反应的介质和/或调节器。由铜绿假单胞菌、超抗原葡萄球菌肠毒素B、内毒素、肥胖、CCl4和亚硫酸盐引起的体内自由基的产生在特定的肺部炎症、脂肪性肝炎和过敏反应中被显示出来。 该小组开发的免疫自旋捕获技术已被应用于帕金森病、吸烟和体内自由基成像中的体内自由基检测。

We have set research priorities to focus on free radical generation in animal models of disease and toxicity for which there is a strong indication of an environmental component. The ways in which environmental agents increase disease risks and toxicity are still poorly understood. In the past our work has been concentrated on the in vivo formation and detection of free radicals from toxic metals and organic compounds and extended into investigations of free radical formation during inflammation caused by lipopolysaccharide itself and in combination with diesel exhaust particles. It is now continued into studies of environmental exotoxins and pathogens with the aim of understanding the basic free radical mechanisms involved in distinctive organ infections, immune disease, and obesity. In vivo spin trapping has been the most successful method for the detection of highly reactive free radical molecules in vivo. The group continued to use spin trapping to solve in vitro biochemical and in vivo toxicological disease problems by using two major approaches for spin trapping, with either ESR detection or antibody recognition and MS identification of the trapped radical. By the use of in vivo spin-trapping methods, these studies test the hypotheses that: 1) free radicals are causative molecules in the complex pathogenesis of lung infections, obesity and allergic response; and 2) specific biochemical pathways are involved in triggering generation of free radicals that may act as mediators and/or modulators of inflammatory reactions associated with human immunity and disease response. Free radical generation in vivo caused by the bacterial pathogen Pseudomonas aeruginosa, superantigen staphylococcal enterotoxin B, the endotoxin LPS, obesity, CCl4, and sulfites has been shown in specific states of lung inflammation, steatohepatitis, and allergic response. Immuno-spin trapping technique developed in this group has been applied to in vivo free radical detection in pakinson's disease, smoking, and in vivo free radical image.