AIR POLLUTANT EFFECTS ON MEDIATORS IN LUNG CELLS

空气污染是呼吸系统疾病的一个重要原因，而且最 常见的气态空气污染物有臭氧(03)、二氧化硫(SO2)和 二氧化氮(NO2)。这项研究的主要目的是阐明 这些气态空气污染物损害鼻腔和鼻腔的细胞机制 并促进这些组织中的炎症。 先前的研究表明，这些上皮细胞在 细胞因子合成对健康和疾病过程的影响 (蛋白质介体)和附加分子的表达 发挥细胞-细胞、细胞-基质和细胞-白细胞黏附的作用 感受器。这项提议的总体假设是空气污染物 直接作用于呼吸道上皮细胞膜，作为一种 结果，调节黏附受体和细胞因子的表达 制作。 提出了一种体外细胞培养的方法，该方法将检测 人和非人灵长类鼻腔和支气管上皮细胞的反应 细胞。将同时使用原代细胞培养和细胞系。第一 目标是定义细胞-细胞和细胞-的合成和表达。 通过这些细胞的底物受体。这些物质包括蛋白多糖、CD44、 CD26和β1整合素。这些受体的结构性生产将 接受检查，以及接触臭氧、二氧化硫和二氧化氮引起的变化。 暴露在单独气体和混合气体中的时间为 周围或接近周围环境的浓度(臭氧，0.1-0.5ppm；二氧化硫：0.5-5ppm； NO2：0.1-0.5ppm)。正在测试的假设是呼吸道 上皮细胞产生维持正常所必需的黏附分子 上皮功能和暴露于气态污染物会改变 这些产物的合成，对组织完整性产生不利影响。这个 第二个目标是测量细胞间黏附的表达 细胞间黏附分子-1(ICAM-1)对鼻腔和支气管细胞的影响 接触O_3、SO_2和NO_2对该受体表达的影响。ICAM-1 IS 上皮细胞上主要的白细胞黏附受体。这个 正在研究的假设是暴露在气态污染物中 上调上皮细胞ICAM-1的表达，从而增强局部 促进白细胞-上皮细胞黏附的炎症反应。这个 第三个目标是检查鼻腔和鼻腔分泌的细胞因子的类型 支气管上皮细胞，如果定性和定量 这些细胞因子的合成会因暴露在臭氧、二氧化硫和二氧化氮中而改变。 正在研究的假设是呼吸道上皮细胞 产生促进局部炎症和暴露的可溶性因子 对污染物的反应刺激了这些事件。这项研究将推动我们的 对呼吸道上皮细胞功能的认识 维持正常的组织完整性，并将确定是否气体 污染物通过调节产生呼吸道炎症和损害 细胞因子和黏附受体的合成。

Air pollution is a significant cause of respiratory disease, and the most common gaseous air pollutants are ozone (O3), sulfur dioxide (SO2) and nitrogen dioxide (NO2). The primary goal of this study is to elucidate cellular mechanisms by which these gaseous air pollutants damage nasal and bronchial epithelial cells and promote inflammation in these tissues. Previous research suggests that these epithelia play an active role in the processes of health and disease through the synthesis of cytokines (protein mediators) and the expression of additional molecules which function as cell-cell, cell-substratum and cell-leukocyte adhesion receptors. The overall hypothesis of this proposal is that air pollutants act directly on the membranes of airway epithelial cells and, as a consequence, modulate adhesion receptor expression and cytokine production. An in vitro cell culture approach is proposed which will examine the responses of human and nonhuman primate nasal and bronchial epithelial cells. Both primary cell cultures and cell lines will be used. The first goal is to define the synthesis and expression of the cell-cell and cell- substratum receptors by these cells. These include proteoglycans, CD44, CD26, and beta1 integrins. Constitutive production of these receptors will be examined as well as changes caused by exposure to O3, SO2 and NO2. Exposures to individual gases and gases in combination will be done at ambient or near ambient concentrations (O3, 0.1-0.5 ppm; SO2: 0.5-5 ppm; NO2: 0.1-0.5 ppm). The hypotheses being tested are that respiratory epithelial cells produce adhesion molecules necessary to maintain normal epithelial function and that exposure to gaseous pollutants alter the synthesis of these products, adversely affecting tissue integrity. The second goal is to measure the expression of intercellular adhesion molecule-1 (ICAM-1) on nasal and bronchial cells and the effects of exposure to O3, SO2 and NO2 on the expression of this receptor. ICAM-1 is the primary leukocyte adhesion receptor on epithelial cells. The hypothesis being examined is that exposure to gaseous pollutants upregulates epithelial cell ICAM-1 expression thus enhancing the local inflammatory response by promoting leukocyte-epithelial adhesion. The third goal is to examine the types of cytokines produced by nasal and bronchial epithelial cells, and if the qualitative and quantitative synthesis of these cytokines is altered by exposure to O3, SO2, and NO2. The hypotheses being examined are that respiratory epithelial cells produce soluble factors which promote local inflammation and that exposure to pollutants stimulates these events. This study will advance our understanding of the functions of respiratory epithelial cells in maintaining normal tissue integrity and will determine whether gaseous pollutants produce respiratory inflammation and damage by modulating cytokine and adhesion receptor synthesis.