O3/ENDOTOXIN COEXPOSURE EFFECT ON AIRWAY EPITHELIUM

O3/内毒素共暴露对气道上皮的影响

基本信息

批准号：
6343602
负责人：
JACK R. HARKEMA
金额：
$ 19.5万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/6343602
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

项目摘要

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。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Enhancement of nasal inflammatory and epithelial responses after ozone and allergen coexposure in Brown Norway rats.

DOI：
10.1093/toxsci/67.2.284
发表时间：
2002-06
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
0
作者：
J. Wagner;J. Hotchkiss;J. Harkema
通讯作者：
J. Wagner;J. Hotchkiss;J. Harkema

Effects of ozone and endotoxin coexposure on rat airway epithelium: potentiation of toxicant-induced alterations.

臭氧和内毒素共同暴露对大鼠气道上皮的影响：毒物引起的改变的增强。

DOI：
10.1289/ehp.01109s4591
发表时间：
2001
期刊：
Environmental health perspectives
影响因子：
10.4
作者：
Wagner,JG;Hotchkiss,JA;Harkema,JR
通讯作者：
Harkema,JR

Endotoxin enhancement of ozone-induced mucous cell metaplasia is neutrophil-dependent in rat nasal epithelium.

在大鼠鼻上皮中，臭氧诱导的粘液细胞化生的内毒素增强是中性粒细胞依赖性的。

DOI：
10.1093/toxsci/60.2.338
发表时间：
2001
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
0
作者：
Wagner,JG;VanDyken,SJ;Hotchkiss,JA;Harkema,JR
通讯作者：
Harkema,JR

Ozone exposure enhances endotoxin-induced mucous cell metaplasia in rat pulmonary airways.

臭氧暴露增强了大鼠肺气道内毒素诱导的粘液细胞化生。

DOI：
10.1093/toxsci/kfg120
发表时间：
2003
期刊：
Toxicological sciences : an official journal of the Society of Toxicology.
影响因子：
0
作者：
Wagner,JamesG;VanDyken,StevenJ;Wierenga,JanelleR;Hotchkiss,JonA;Harkema,JackR
通讯作者：
Harkema,JackR

Effects of pre-existing rhinitis on ozone-induced mucous cell metaplasia in rat nasal epithelium.

已有鼻炎对臭氧诱导的大鼠鼻上皮粘液细胞化生的影响。