OXIDANT AIR POLLUTANT EFFECTS ON LUNG LINING FLUID(S)

有毒气体臭氧、二氧化氮和香烟烟雾(CS)会导致肺损伤。这个 损伤的细胞和分子机制复杂，但氧化剂 反应被认为是起主要作用的。呼吸道 上皮衬里液体(RTLF)是最早的生物系统之一 接触到吸入的气体。RTFL包含许多不同的 抗氧化剂，包括粘蛋白、尿酸、α-生育酚、抗坏血酸、 和谷胱甘肽。尽管人们对个体的反应知之甚少 单独的抗氧化剂和氧化剂，人们对其了解很少 红景天不同部位的综合抗氧化防御作用 呼吸道。RTLFS不仅可以防止氧化损伤 基础细胞，但其成分的氧化可能会产生 细胞毒性产品。此外，它们的几种蛋白质和脂肪 成分具有特定的功能，如抑制弹性蛋白酶的能力。 以及降低表面张力的能力。申请者将应用一种策略 其中不同抗氧化剂的时间损失被量化为 结构和功能蛋白与脂质损伤发病的关系 暴露于O_3、NO_2和CS的RTLf。氧化型实时荧光材料的细胞效应 还将接受检查。具体目标是：(I)确定 呼吸不同部位RTLF中存在的抗氧化剂 (Ii)确定RTLFS中最重要的抗氧化剂， 保护蛋白质和脂质免受臭氧、亚硝酸盐和CS的损害， 单独或组合；(Iii)研究RTLF氧化的影响 对其细胞毒性和生化功能的影响。高度- 将使用灵敏、特异的检测方法来检测抗氧化剂、脂质 蛋白质的过氧化和氧化损伤。了解 抗氧化剂在RTLFS中的综合保护作用可能会提供新的 对生物化学和细胞事件发生顺序的洞察 暴露在有毒气体中后的呼吸道。这可能会导致 制定保护性治疗干预战略和 臭氧损伤的“生物标志物”。

The toxic gases O3, NO2 and cigarette smoke (CS) cause lung damage. The cellular and molecular mechanisms of the damage are complex, but oxidant reactions are thought to play a major role. The respiratory tract epithelial lining fluids (RTLFs) are among the first biological systems to come into contact with inhaled gases. RTLFs contain many different antioxidants, including mucin, uric acid, alpha-tocopherol, ascorbic acid, and glutathione. Although much is known about the reactions of individual isolated antioxidants with oxidants, very little is known about the integrated antioxidant defenses of RTLFs from different parts of the respiratory tract. RTLFs may not only protect against oxidative injury to underlying cells, but oxidation of their constituents may generate cytotoxic products. In addition, several of their protein and lipid constituents have specific functions, such as elastase-inhibiting capacity and surface tension-lowering ability. The applicants will apply a strategy in which temporal losses of different antioxidants are quantitated in relation to the onset of structural and functional protein and lipid damage in RTLFs exposed to O3, NO2 and CS. The cellular effects of oxidized RTLFs will also be examined. The specific aims are: (i) to identify the antioxidants present in RTLFs from different parts of the respiratory tract; (ii) to identify the most important antioxidants in RTLFs that can protect the proteins and lipids present against damage by O3, NO2 and CS, singly or in combination; (iii) to study the effects of oxidation of RTLF components upon their cytoxicity and their biochemical functions. Highly- sensitive, specific assays will be used to measure antioxidants, lipid peroxidation and oxidative damage to proteins. Understanding the integrated protective role of antioxidants in RTLFs may well provide new insights into the sequence of biochemical and cellular events occurring in the respiratory tract after exposure to toxic gases. This may lead to the development of strategies for protective therapeutic interventions and of "biomarkers" for O3-induced damage.