ROLE OF AIRWAY SURFACE LIQUID IN AIRWAY DEFENSE

未能了解慢性阻塞性肺疾病的发病机制反映了 第二部分，我们对呼吸道表面液体正常生理的忽视 (ASL)。项目I提出了旨在区分两种类型的实验 声称描述自闭症正常生理学的相互竞争的理论 并测量与实验相连接的传输技术 新型细胞培养制剂。具体目标1将利用大量和 小气道培养和共聚焦显微镜研究生理学和 在微观水平上的ASL。关键问题将集中在描述 ASL是否有明显的粘液和睫状液层， 水(PCL)是否沿轴向向口腔沿呼吸道表面移动 或者不去。具体目标2侧重于特征和相互关系 大小呼吸道上皮细胞的功能。全面分析 与盐分分泌和吸收相关的基因的表达 执行以测试潜在的区域和区域内模式 吸收(近端呼吸道)与分泌物(腺体，远端) 细支气管炎)。填充的平面和新型生物纤维制剂 来自显微解剖的细支气管壁和大气道的上皮细胞将 以离子渗透、水的途径为特征 渗透率(L/p)、体积吸收(J/v)和表面液体离子 组成。从培养的制剂中选择的参数将是 与新鲜切除的准备工作得出的数据进行比较。最后， 具体目标3将测量CFTR突变对这些 功能。离子渗透途径、L/p和J/v将在 培养准备来自CF大的，如果可能的话，小的呼吸道。一个 主要目标将是测量区分 在相互竞争的理论之间：(1)ASL构成；(2)存在/ 等张J/V比率及其与有效粘液清除的关系。 因此，该项目应开发新的信息集成本地和 健康和发展关键信息的区域内ASL代谢 关于在这些促进感染的功能中存在的CF型特异性缺陷。

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.