POLLUTANT INDUCED MUCOCILIARY DYSFUNCTION IN THE AIRWAYS

污染物引起的气道粘液纤毛功能障碍

基本信息

批准号：
3250191
负责人：
Adam Wanner
金额：
$ 16.82万
依托单位：
MOUNT SINAI MEDICAL CENTER (MIAMI BEACH)
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-09-01 至 1991-06-30
项目状态：
已结题

项目摘要

It is well recognized that short term and long term exposures to gaseous pollutants including ozone can alter the structure and function of the airways. However, the exact mechanisms by which airway injury leads to abnormal function remains to be clarified. We have previously shown (years 04 and 05) that inhaled ozone impairs airway mucus clearance, that this impairment is primarily due to a defect in epithelial secretion, that it is temporarily related to airway inflammation and that it can be mimicked by selected inflammatory mediators. We now propose to test the central hypothesis that all three manifestations of ozone-induced airway injury, i.e. airway smooth muscle hyperresponsiveness, mucosal dysfunction, and microvascular hyperemia and leakage are causally related to airway inflammation. With a set of in vivo and in vitro studies involving sheep exposed to intermediate levels of ozone on a short-term basis (1 ppm for 2 hrs), we will 1) determine if markers of inflammation (leukocyte, chemical mediators) associated with airway hyperresponsiveness in vivo can produce airway smooth muscle hyperesponsiveness in vitro and this can be modified by anti-inflammatory agents, 2) identify the component of mucociliary interaction which is most severely impaired and determine which imflammatory mediators play a putative role, 3) demonstrate the possibility of sequential activation of inflammatory products mediating airway epithelial cell dysfunction, and 4) characterize the role of inflammatory mediators in the microvascular responses of the airway mucosa. Long term exposure to ozone (0.5 ppm, 4 hrs/day, 5 days/week, 6 weeks) will be employed to test the secondary hypothesis that disruption of the airway epithelium causes airway smooth muscle hyperresponsiveness because of a decreased production of epithelium derived relaxant factors. By interrelating the cytologic and biochemical indices of airway inflammation with the various physiologic endpoints and by the use of appropriate antagonists, we expect to obtain interpretable data with which to test the basic premise underlying this proposal. We believe that the results of this investigation will provide useful information on the pathogenesis of ozone-induced airway injury, and that some of this information can be extrapolated to airway disease in general and form the basis for pharmacologic intervention.

众所周知，短期和长期暴露包括臭氧在内的气态污染物可以改变结构，气道的功能。但是，确切的机制哪些气道损伤导致功能异常仍然是澄清。我们以前显示了吸入的（04年和05年）臭氧会损害气道粘液间隙，这种障碍是主要是由于上皮分泌缺陷，是暂时与气道炎症有关，可能是被选定的炎症介质模仿。我们现在建议测试中心假设，即所有三种表现臭氧引起的气道受伤，即气道平滑肌反应性过高，粘膜功能障碍和微血管充血和泄漏与气道有因果关系炎。一组体内和体外研究涉及短期暴露于中间臭氧的绵羊基础（2 hrs 1 ppm），我们将1）确定是否标记炎症（白细胞，化学介质）气道高反应性体内可以使气道平滑产生气道体外肌肉过度肌肉过敏，这可以通过抗炎剂，2）确定粘膜纤毛相互作用，最严重受损，确定哪些不发炎的介体起着推定的作用，3）证明了顺序激活的可能性介导气道上皮细胞的炎症产品功能障碍和4）表征炎症的作用气道粘膜微血管反应中的介体。长期暴露于臭氧（0.5 ppm，4小时/天，5天/周，6 几周）将用于检验次要假设气道上皮的破坏会导致气道平滑肌由于产生的产生减少上皮衍生的松弛因子。通过相互关联气道炎症的细胞学和生化指数各种生理终点以及使用适当的对手，我们希望获得可解释的数据测试该提案的基本前提。我们相信这项调查的结果将提供有关的有用信息臭氧引起的气道损伤的发病机理，其中一些总体上，这些信息可以推断到气道疾病并构成药理干预的基础。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effects of P. aeruginosa-derived bacterial products on tracheal ciliary function: role of O2 radicals.

DOI：
10.1152/ajplung.1991.260.2.l61
发表时间：
1991-02
期刊：
The American journal of physiology
影响因子：
0
作者：
J. Jackowski;Z. Szépfalusi;D. Wanner;Z. V. Seybold;M. Sielczak;I. Lauredo;T. Adams;William M. Abraham;Adam Wanner
通讯作者：
J. Jackowski;Z. Szépfalusi;D. Wanner;Z. V. Seybold;M. Sielczak;I. Lauredo;T. Adams;William M. Abraham;Adam Wanner

Effect of ozone on the postnatal development of lamb mucociliary apparatus.

臭氧对羔羊粘液纤毛器产后发育的影响。