O3/ENDOTOXIN COEXPOSURE EFFECT ON AIRWAY EPITHELIUM

O3/内毒素共暴露对气道上皮的影响

• 批准号: 6139270
• 负责人: JACK R. HARKEMA
• 金额: $ 18.04万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6139270
• 关键词: air pollution; bronchial mucus; cell population study; cell proliferation; endotoxins; gene expression; histology; inflammation; laboratory rat; metaplasia; mucins; neutrophil; ozone; respiratory epithelium; secretion; toxicant interaction

DESCRIPTION (Adapted from the Investigator's Abstract): The goal of this project is to understand how inflammation induced by the inhalation of bacterial endotoxin affects the response of the airway epithelium to ozone, the principal oxidant air pollutant in photochemical smog. Each toxicant alone causes airway inflammation that is followed by mucous cell metaplasia characterized by proliferation of mucus-secreting cells in regions of the airway that normally contain no or few secretory cells. Mucous cell metaplasia is a common pathologic feature of airway diseases, such as chronic bronchitis, cystic fibrosis, and asthma. The consequences of co-exposure to these two airborne pollutants have not been fully explored. These studies will focus on the effects of co-exposure on the pathogenesis of: 1) the initial epithelial cell injury and inflammation, and 2) the subsequent induction of mucous cell metaplasia associated with mucin synthesis and secretion. Experiments will extend preliminary findings indicating that co-exposure of rats to endotoxin and ozone will induce greater premetaplastic lesions (airway inflammation and epithelial cell loss) than exposure to either toxicant alone. Studies will determine if the magnitude of the premetaplastic epithelial lesions is dependent on the initial inflammatory cell response. Studies will also focus on the pathogenesis and severity of the mucous cell metaplasia caused by co-exposure to ozone and endotoxin by determination of nasal and bronchial airways epithelial differentiation, increased mucin mRNA, hypersecretion of mucins. The role of ozone/endotoxin-induced inflammatory cell response in the overproduction of airway mucus will be examined. A combination of morphometric, histochemical, immunochemical, and molecular techniques will be used to identify temporal alterations in epithelial cell populations, intraepithelial mucosubstances, mucin gene expression, and mucin secretion in nasal and pulmonary airways. The results from these studies will reveal interactive effects of co-exposure on the mucous apparatus of the nasal and pulmonary airway epithelium, and the role of neutrophils in the amplification of airway alterations due to co-exposure to ozone and endotoxin.

描述（根据调查员的摘要改编）：目的 项目是了解如何通过吸入炎症引起的 细菌内毒素会影响气道上皮对臭氧的反应， 光化学烟雾中的主要氧化剂空气污染物。 每个有毒物质 仅引起气道炎症，其次是粘液细胞化生 以粘液分泌细胞在该区域的扩散 通常不包含或几个分泌细胞的气道。 粘液细胞 Metaplasia是气道疾病的常见病理特征，例如 慢性支气管炎，囊性纤维化和哮喘。 后果 尚未完全探讨这两种空气传播污染物的共同曝光。 这些研究将集中于共曝光对发病机理的影响 ：1）初始上皮细胞损伤和炎症，2） 随后诱导与粘蛋白相关的粘液细胞化生 合成和分泌。 实验将扩展初步发现 表明大鼠对内毒素和臭氧的共同暴露会诱导 较大的前塑性病变（气道炎症和上皮细胞 损失）比仅接触任何一种有毒物质。 研究将确定是否是否 前塑性上皮病变的大小取决于 初始炎症细胞反应。 研究还将集中于 由 通过确定鼻和支气管的共同暴露于臭氧和内毒素 气道上皮分化，粘蛋白mRNA升高，过度分泌 粘蛋白。 臭氧/内毒素诱导的炎症细胞反应在 将检查气道粘液的过量生产。 组合 形态学，组织化学，免疫化学和分子技术将 用于识别上皮细胞种群的时间改变， 上皮内粘液固定，粘蛋白基因表达和粘蛋白分泌 在鼻和肺气道中。 这些研究的结果将揭示 共曝光对鼻粘液仪的互动效应和 肺气道上皮，中性粒细胞在 由于臭氧的共曝光而扩大气道改变 内毒素。