POLLUTANT INDUCED MUCOCILIARY DYSFUNCTION IN THE AIRWAYS

污染物引起的气道粘液纤毛功能障碍

• 批准号: 3250188
• 负责人: Adam Wanner
• 金额: $ 14万
• 依托单位: MOUNT SINAI MEDICAL CENTER (MIAMI BEACH)
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3250188
• 关键词: acid base balance; biological fluid transport; breath tests; bronchial mucus; bronchoscopy; cell migration; cilium /flagellum motility; diagnostic respiratory lavage; electron microscopy; environmental toxicology; excretion; histology; infant animal; inflammation; leukocytes; leukotrienes; mass spectrometry; mature animal; nonblood rheology; pollution related respiratory disorder; prostaglandins; pulmonary edema; radiography; radioimmunoassay; respiratory airflow disorder; respiratory disorder chemotherapy; respiratory epithelium; respiratory function; respiratory gas analyzer; statistics /biometry; trachea

It has been previously shown that short-term and long-term exposures to gaseous pollutants alter mucosal function in the airways. The mechanisms underlying the associated depression in mucociliary clearance have been partially elucidated. In particular, it has been shown that changes in mucosal secretion rather than primary ciliary dysfunction are responsible for this defect. However, it is not known if the observed functional changes are caused by a direct effect of the pollutant on the mucociliary apparatus or indirectly by the concomitant airway inflammation in analog to the previously shown role of airway inflammation in pollutant induced airway hyperreactivity. The purpose of this proposal is therefore to determine in sheep if 1) the impairment of mucosal function by short-term low-level O3 exposure (0.5-1 ppm for 2 hours) is associated with leukocytes influx into the airway, 2) the prevention of leukocyte migration also prevents pollutant induced mucosal dysfunction, 3) mucosal dysfunction is related to inflammatory mediators, 4) the newborn airway is more vulnerable to pollutant induced mucosal dysfunction than the adult airway, and 5) pollutant induced mucosal dysfunction alters bacterial clearance in central airways and if the bacterial clearance is modified by the inflammatory response. The studies will be carried out in lambs and adult sheep and focus on the trachea. Mucosal function will be assessed in vivo by the determination of mucociliary transport with a radiographic technique and airway wall water content using a double gas bolus method to detect mucosal edema formation. Airway inflammation will be assessed by tracheal lavage and biopsy, and the role of chemical mediators by mediator assay in lavage fluid, and the use of appropriate antagonists. A bacterial aerosol will be used to determine the persistence of viable bacteria in the trachea. To suppress the inflammatory response, pluronic F-68, a potent inhibitor of leukocyte migration will be used. We expect these studies to delineate the role of inflammation in the impairment of mucosal function by O3. The results might form the basis for pharmacologic modification of pollutant induced mucociliary dysfunction.

以前已经表明，短期和长期暴露 气体污染物改变气道中的粘膜功能。 机制 粘膜缩减清除的基本抑郁症已是 部分阐明。 特别是，已经显示出变化 粘膜分泌而不是原发性睫状功能障碍是负责的 对于这个缺陷。 但是，尚不清楚观察到的功能是否 变化是由污染物对粘膜纤毛的直接作用引起的 仪器或间接通过类似的气道炎症 先前显示的气道炎症在污染物诱导中的作用 气道高反应性。 因此，该提议的目的是 确定绵羊在1）短期粘膜功能的损害 低水平的O3暴露（0.5-1 ppm，持续2小时）与白细胞有关 涌入气道，2）预防白细胞迁移 防止污染物诱导的粘膜功能障碍，3）粘膜功能障碍是 与炎症介质有关，4）新生儿气道更脆弱 污染物引起的粘膜功能障碍比成人气道，5） 污染物诱导的粘膜功能障碍改变中央细菌清除率 气道以及细菌清除是否通过炎症来改变 回复。 研究将在羔羊和成年绵羊和 专注于气管。 粘膜功能将在体内评估 用射线照相技术和 气道墙水含量使用双气大注法检测粘膜 水肿形成。 气道炎症将通过气管灌洗来评估 和活检，以及化学介质在灌洗中的作用 流体和适当拮抗剂的使用。 细菌气溶胶将是 用于确定气管中可行细菌的持久性。 到 抑制炎症反应，Pluronic F-68，一种有效的抑制剂 将使用白细胞迁移。 我们希望这些研究能够描述 O3炎症在粘膜功能受损中的作用。 这 结果可能构成污染物药理修饰的基础 诱导的粘纤毛功能障碍。