AIR POLLUTANT EFFECTS ON MEDIATORS IN LUNG CELLS

空气污染物对肺细胞介质的影响

• 批准号: 2226820
• 负责人: Daniel L Luchtel
• 金额: $ 30.93万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226820
• 关键词: CD antigens; Macaca nemestrina; air pollution; antiinflammatory agents; cell adhesion molecules; cellular pathology; cytokine; environmental toxicology; flow cytometry; free radical oxygen; gas; human subject; inflammation; integrins; neutrophil; nitrogen oxides; ozone; pollutant interaction; pollution related respiratory disorder; proteoglycan; receptor expression; respiratory epithelium; respiratory toxin; sulfur compounds; tissue /cell culture

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.

空气污染是呼吸道疾病的重要原因， 常见的气态空气污染物是臭氧（O3）、二氧化硫（SO2）和 二氧化氮（NO2）。本研究的主要目的是阐明 这些气态空气污染物通过细胞机制损害鼻和 支气管上皮细胞并促进这些组织中的炎症。 以前的研究表明，这些上皮细胞在肿瘤的发生发展中起着积极的作用。 健康和疾病的过程通过细胞因子的合成 （蛋白质介质）和表达额外的分子， 细胞-细胞、细胞-基质和细胞-白细胞粘附 受体。这项建议的总体假设是， 直接作用于气道上皮细胞膜， 结果，调节粘附受体表达和细胞因子 生产 提出了一种体外细胞培养方法，该方法将检查 人和非人灵长类鼻和支气管上皮细胞的反应 细胞将使用原代细胞培养物和细胞系。第一 目的是定义细胞-细胞和细胞- 这些细胞的基质受体。这些包括蛋白聚糖，CD 44， CD 26和β 1整合素。这些受体的组成性产生将 以及暴露于O3、SO2和NO2引起的变化。 暴露于单个气体和混合气体的时间为 环境或接近环境浓度（O3，0.1-0.5 ppm; SO2：0.5-5 ppm; NO2：0.1-0.5 ppm）。正在测试的假设是， 上皮细胞产生粘附分子， 上皮功能以及暴露于气态污染物会改变 这些产物的合成，不利地影响组织完整性。的 第二个目标是测量细胞间粘附的表达， 分子-1（ICAM-1）对鼻和支气管细胞的影响以及 暴露于O3、SO2和NO2对该受体表达的影响。ICAM-1是 上皮细胞上的主要白细胞粘附受体。的 正在研究的假设是，暴露于气态污染物 上调上皮细胞ICAM-1表达，从而增强局部 通过促进白细胞-上皮细胞粘附而引起炎症反应。的 第三个目标是检查鼻和鼻腔分泌物产生的细胞因子的类型， 支气管上皮细胞，如果定性和定量 这些细胞因子的合成因暴露于O3、SO2和NO2而改变。 正在研究的假设是， 产生促进局部炎症的可溶性因子， 污染物刺激了这些事件。这项研究将促进我们的 了解呼吸道上皮细胞的功能 维持正常组织的完整性，并将确定是否有气体 污染物通过调节呼吸道炎症和损伤， 细胞因子和粘附受体合成。