AIR PARTICLES CAUSE DEATH IN ANIMALS WITH LUNG DISEASE

空气颗粒导致患有肺病的动物死亡

• 批准号: 6467583
• 负责人: John J Godleski
• 金额: $ 13.47万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6467583
• 关键词: air pollution; animal morbidity; animal mortality; chronic bronchitis; cytokine; disease /disorder model; eicosanoid metabolism; environmental health; environmental toxicology; hypoventilation; immunocytochemistry; inflammation; interleukin 1; laboratory rat; particle; pathologic process; pollutant interaction; pollution related respiratory disorder; respiratory airflow disorder; respiratory function; tumor necrosis factor alpha

This project will define the effects of concentrated air particles in an animal model of chromic bronchitis. It will determine the role of concentration vs composition in producing adverse effects. The project focuses upon discovery of mechanisms of death and morbidity caused by ambient air particles in animals with pre-existing pulmonary inflammation and airway hyperresponsiveness. Specific aims are: 1) To define the extent of mortality resulting from exposure to various levels of concentrated ambient air particles (CAPs) using normal adult rats and rats with chronic bronchitis; and 2) To determine the mechanisms by which inflammation contributes to mortality and morbidity from exposure to CAPs in the rat model of chronic bronchitis, and 3) To characterize the degree of airway obstruction and hypoventilation present in rats with chronic bronchitis that could lead to increased morbidity and mortality with exposure to CAPs. To assess effects of ambient air particles, animals will be exposed using the Harvard Ambient Particulate Concentration (HAPC), a newly developed device that can increase ambient particle concentrations up to thirty times ambient levels without changing the physical or chemical characteristics of the particles. The exposed animal populations will model human populations and adverse effects including increased mortality that have been identified epidemiologically. Concentrating airborne particles for use in exposures will permit the populations studied in the laboratory to be of a size to see the modeled effect and a size unable to test mechanistic hypotheses. Exposures will take place in Boston, MA, which has a typical fine particle urban aerosol ranging from 5-15 gu/m3 with transported sulfur-containing acidic particles during the summer and local combustion product particulate in winter. With Core support, extensive physical, chemical, andmicrobiologic analysis of the exposure aerosol will be carried out with correlation between these parameters and biologic responses of the animals. Established physiologic methods will probe airway responses and their mechanisms. Cell and molecular biology methods will test mechanistic hypotheses on the role of pro-inflammatory mediators in the development of morbidity and mortality. The novel application of of sophisticated techniques in our proposed studies will offer new insights into mechanisms of toxicity of ambient air particles.

该项目将定义集中空气颗粒的影响 染色性支气管炎的动物模型。 它将决定角色 浓度与成分产生不良反应。 这 项目的重点是发现死亡机制和 动物中的环境空气颗粒引起的发病率 预先存在的肺部炎症和气道 反应性过高。 具体目的是：1）定义 暴露于各种浓缩水平的死亡率 使用正常的成年大鼠和大鼠的环境空气颗粒（盖） 慢性支气管炎； 2）确定其机制 炎症导致死亡率和发病率 到慢性支气管炎大鼠模型中的帽子，3） 表征气道阻塞和不足的程度 存在于慢性支气管炎的大鼠中，可能导致增加 暴露于帽子的发病率和死亡率。 评估效果 环境空气颗粒，将使用哈佛暴露动物 环境颗粒浓度（HAPC），新开发 可以将环境颗粒浓度提高到最高的设备 三十倍的环境水平而不改变身体或 颗粒的化学特征。 暴露的动物 人口将建模人口和不利影响 包括已确定的死亡率增加 流行病学。 集中空气颗粒用于 暴露将允许实验室研究的人群 可以看到建模效果和无法测试的尺寸的大小 机械假设。 暴露将在马萨诸塞州波士顿举行 它的典型细粒子城市气溶胶范围为5-15 GU/M3在含有硫硫酸的酸性颗粒的GU/M3期间 冬季夏季和局部燃烧产品颗粒物。 和 核心支持，广泛的物理，化学和微生物学 暴露气溶胶的分析将与相关性进行 在这些参数和动物的生物反应之间。 建立的生理方法将探测气道反应，并 他们的机制。 细胞和分子生物学方法将测试 关于促炎性介体作用的机械假设 在发病和死亡率的发展中。 小说 在我们的拟议研究中，精致技术的应用 将提供有关环境空气毒性机制的新见解 颗粒。