ROLE OF AIRWAY SURFACE LIQUID IN AIRWAY DEFENSE

气道表面液体在气道防御中的作用

• 批准号: 6110932
• 负责人: Richard Charles Boucher
• 金额: $ 22.26万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110932
• 关键词: animal tissue; biological fluid transport; biomaterial development /preparation; bronchioles; chloride channels; cystic fibrosis; fluidity; gene expression; gene mutation; laboratory mouse; membrane permeability; mucus; respiratory epithelium; respiratory function; secretion; tissue /cell culture; tissue engineering

The failure to understand the pathogenesis of CF lung disease reflects, in part, our ignorance of the normal physiology of airway surface liquids (ASL). Project I proposes experiments designed to distinguish between two competing theories that purport to describe the normal physiology of ASL and measure the transport technologies interfaced with experiments using novel cell culture preparations. Specific Aim 1 sill utilize large and small airway cultures and confocal microscopy to study the physiology and ASL at the microscopic level. Key questions will focus on delineating whether there are distinct mucus and periciliary liquid layers with ASL, and whether water (PCL) moves axially toward the mouth up airways surfaces or not. Specific Aim 2 focuses on characterizing and interrelation functions of small with large airway epithelia. A comprehensive analysis of expression of genes relevant to salt secretion and absorption will be performed to test for potential regional and intra-regional patterns of absorption (proximal airways) versus secretion (glands, ?distal bronchioles). Planar and novel biofiber preparations populated with epithelia derived from microdissected bronchioles and large airways will be characterized with respect to routes of ion permeation, water permeability (L/p), volume absorption (J/v), and surface liquid ion composition. Selected parameters from the cultured preparations will be compared to data derived from freshly excised preparations. Finally, Specific Aim 3 will measure the effects of mutations in CFTR on these functions. Routes of ion permeation, L/p, and J/v will be measured in culture preparations from CF large and, if possible, small airways. A primary goal will be to measure the two parameters that discriminate between the competing theories: (1) ASL composition; and (2) existence of/ rates os isotonic J/v and its relationship to effective mucus clearance. Thus, this project should develop novel information integrating local and intra-regional ASL metabolism in health and develop key information regarding CF-specific defects in these functions that promote infection.

未能了解CF肺病的发病机制反映了， 一方面，我们对气道表面液体的正常生理学的无知 （美国手语）。项目I提出了旨在区分两种 旨在描述ASL正常生理学的竞争理论 并测量与实验相结合的运输技术， 新的细胞培养制剂。具体目标1仍然利用大型和 小气道培养和共聚焦显微镜来研究生理学和 在微观层面上。关键问题将集中在描绘 ASL是否有明显的粘液层和纤毛周液层， 以及水（PCL）是否轴向地朝向嘴向上气道表面移动 或不.具体目标2侧重于表征和相互关系 小气道上皮与大气道上皮的功能。全面分析 与盐的分泌和吸收相关的基因的表达， 测试潜在的区域和区域内模式， 吸收（近端气道）与分泌（腺体，？远侧 细支气管）。平面和新型生物纤维制剂， 来自显微解剖的细支气管和大气道的上皮细胞将 其特征在于离子渗透、水 渗透率（L/p）、体积吸收（J/v）和表面液体离子 混合物.从培养制备物中选择的参数将是 与来自新鲜切除的制备物的数据进行比较。最后， 具体目标3将测量CFTR突变对这些细胞的影响。 功能协调发展的离子渗透途径、L/p和J/v将在 从CF大气道和小气道（如果可能）制备培养物。一 主要目标是测量区分 竞争理论之间：（1）ASL组成;和（2）/的存在 速率os等渗J/v及其与有效粘液清除的关系。 因此，该项目应开发新的信息， 区域内ASL代谢在健康和发展关键信息 关于CF特异性缺陷在这些功能，促进感染。