EFFECTS OF OZONE ON AIRWAY MUCOUS CELLS

臭氧对气道粘液细胞的影响

• 批准号: 2228620
• 负责人: JACK R. HARKEMA
• 金额: $ 11.98万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2228620
• 关键词: antiinflammatory agents; asthma; bronchial mucus; chronic bronchitis; diagnostic respiratory lavage; enzyme linked immunosorbent assay; gene expression; histochemistry /cytochemistry; laboratory rat; lung; messenger RNA; metaplasia; mucins; nonhuman therapy evaluation; ozone; pollution related respiratory disorder; respiratory disorder chemotherapy; secretion

The health effects of chronic ozone exposure are unknown. Because of obvious ethical problems, chronic exposures of human volunteers to ozone in controlled environmental chambers will not be done. Therefore, the health risks from chronic ozone exposure must be estimated by using data from chronic animal exposure studies. Thus, the proposed research will investigate the effects of chronic ozone exposures on the mucous apparatus in the upper and lower airways of the rats. Rats will be exposed 8 h/day, 7 days/wk for 1, 3, 6, or 12 mo to 0.25, 0.5, or 1 ppm ozone. These animals will be sacrificed immediately (Specific Aim 1), and at 1 mo, 3 mo, or 6 mo after the end of the exposure (Specific Aim 2) to monitor the persistence of the pathology. Nasal and lung lavage fluids will be analyzed to determine the amount of secreted mucin using an enzyme-linked immunosorbant assay. Also, the amount of intracellularly stored mucosubstances in nasal and pulmonary airways will be estimated using histochemistry and morphometry. Mucin gene expression in nose and lung will be assessed by quantifying airway mucin mRNA. Using the same methods, a third Specific Aim will be to determine the effects of ozone exposures on the recovery of rat pulmonary airways from a hypersecretory condition similar to that in patients with chronic bronchitis or asthma. In addition, we will determine if anti-inflammatory drugs speed the recovery from ozone-induced mucous cell metaplasia (Specific Aim 4). The proposed studies will define 1) this airway epithelial lesion induced by chronic ozone, 2) the time course of recovery from this lesion, 3) the effects of ozone on hypersecretory airways, and 4) the effectiveness of anti- inflammatory drugs in attenuating the lesion. Further, our ability to determine the time points at which mucin synthesis (mRNA induction) and hypersecretion (mucin release into airway lumens) occur will open the way for future studies into mechanisms mediating these changes.

慢性臭氧暴露的健康影响尚不清楚。由于 明显的道德问题，人类志愿者的慢性暴露于臭氧 在受控的环境室中，不会完成。因此， 必须通过使用数据来估算慢性臭氧暴露的健康风险 来自慢性动物暴露研究。因此，拟议的研究将 研究慢性臭氧暴露对粘液设备的影响 在大鼠的上和下气道中。大鼠将暴露8小时/天， 1、3、6或12 mo至0.25、0.5或1 ppm臭氧的7天/周。这些 动物将立即牺牲（特定目标1），在1 mo，3 MO，或接触结束后6个月（特定目标2）以监视 病理的持久性。鼻和肺灌洗液将是 分析以确定使用酶连接的分泌粘蛋白的量 免疫吸附测定法。另外，细胞内存储的量 使用鼻和肺气道中的粘液固定 组织化学和形态计量学。鼻和肺中的粘蛋白基因表达 将通过量化气道粘蛋白mRNA进行评估。使用相同的方法， 第三个特定目的是确定臭氧暴露的影响 关于从大量转化状况中恢复大鼠肺气道 与慢性支气管炎或哮喘患者相似。在 此外，我们将确定抗炎药是否加快恢复 来自臭氧诱导的粘液细胞化生（特定目标4）。 提议 研究将定义1）慢性诱导的这种气道上皮病变 臭氧，2）从这种病变中恢复的时间过程，3） 臭氧在超偏呼吸道上，4）抗臭氧的有效性 炎症药物减弱病变。此外，我们的能力 确定粘蛋白合成（mRNA诱导）和 过度分泌（粘蛋白释放到气道流明）将开放 为了将来研究介导这些变化的机制。