TOXIC OXYGEN SPECIES MEDIATED ACUTE LUNG INJURY

本提案的总体目标是研究 部分还原的氧类介导肺细胞损伤。 主动脉瓣和 肺动脉内皮细胞和II型肺泡上皮细胞 将被用作体外模型，因为存在两种体外模型的数据库。 这些细胞类型对氧化应激的体外和体内反应。 到 为了实现这一点，拟议的研究旨在阐明生物化学 氧化性肺损伤的机制。 因此，以下具体目标将 应处理： 1.建立内皮细胞和II型肺泡上皮细胞 自由基介导的肺损伤研究的培养模型。 2.研究细胞质，膜和细胞外产生的游离 自由基的EPR技术。 3.自由基的细胞形成将被监测和调节 使用高氧和电子传递的解偶联剂。 4.自由基的细胞代谢将使用自由基研究 清除剂和脂质体介导的细胞内 抗氧化防御 5.自由基损伤的细胞指数和损伤的调节将是 研究使用代谢指标和EPR测量的结构 膜微区的变化。 这项研究提案代表了肺细胞生物学和 复杂的光谱方法来识别 特定的自由基及其对膜结构的影响。 使用脂质体的抗氧化防御的药理学操作 含有超氧化物歧化酶或过氧化氢酶将是潜在有益的 在许多代谢情况下。 最后，完成上述具体的 目的将提供深入了解氧化剂肺损伤的病因。

The overall goal of this proposal is to study the mechanisms by which partially reduced oxygen species mediate lung cell injury. Aortic and pulmonary artery endothelial cells and type II aveolar epithelial cells will be used as in vitro models because a data base exists for both the in vitro and in vivo responses of these cell types to oxidant stress. To accomplish this, proposed studies are designed to illuminate biochemical mechanisms of oxidant lung injury. Thus, the following specific aims will be addressed: 1. Establish an endothelial cell and type II aveolar epithelial cell culture models for the study of free radical mediated lung injury. 2. Study cytoplasmically, membrane and extracellularly generated free radicals using EPR techniques. 3. Cellular formation of free radicals will be monitored and modulated using hyperoxia and uncouplers of electron transport. 4. Cellular metabolism of free radicals will be studied using free radical scavengers and by liposome mediated augmentation of intracellular antioxidant defenses. 5. Cellular indices of free radical injury and modulation of injury will be studied using metabolic indicators and EPR measurement of structural changes in membrane microdomains. This research proposal represents a combination of lung cell biology and sophisticated spectroscopic approaches towards the identification of specific free radicals and their affects on membrane structure. Pharmacological manipulation of antioxidant defenses using liposomes containing superoxide dismutase or catalase will be potentially beneficial in many metabolic situations. Finally, completion of the above specific aims will provide insight into the etiology of oxidant lung injury.