OXIDANT AIR POLLUTANT EFFECTS ON LUNG LINING FLUID(S)

有毒气体O3、NO2和香烟烟雾（CS）会导致肺损伤。 的 损伤的细胞和分子机制是复杂的，但氧化剂 反应被认为起主要作用。 呼吸道 上皮细胞衬液（RTLF）是第一个生物系统， 与吸入的气体接触。 RTLF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。 虽然我们对个体的反应已经有了很多了解， 分离的抗氧化剂与氧化剂，很少有人知道， 来自不同部位的RTLF的综合抗氧化防御 呼吸道 RTLFs不仅可以防止氧化损伤， 但其成分的氧化可能会产生 细胞毒性产品。 此外，它们的一些蛋白质和脂质 成分具有特定的功能，例如弹性蛋白酶抑制能力， 和降低表面张力的能力。 申请人将采用一种策略 其中定量不同抗氧化剂的暂时损失， 与结构和功能性蛋白质和脂质损伤的发生的关系 RTLF暴露于O3、NO2和CS。 氧化RTLFs的细胞效应 也将被审查。 具体目标是：（一）确定 抗氧化剂存在于呼吸道不同部位的RTLF中， 道;（ii）确定RTLF中最重要的抗氧化剂， 保护蛋白质和脂质免受O3，NO2和CS的损害， 单独或组合;（iii）研究RTLF氧化的影响 它们的细胞毒性和生化功能。 非常- 灵敏、特异的检测将用于测量抗氧化剂、脂质 蛋白质的过氧化和氧化损伤。 了解 抗氧化剂在RTLF中的综合保护作用可能会提供新的 深入了解生物化学和细胞事件发生的顺序， 暴露于有毒气体后的呼吸道。 这可能导致 制定保护性治疗干预战略， O3引起的损伤的“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.