LUNG EPITHELIAL TRANSPORT PROPERTIES AND ALVEOLAR EDEMA

拟议研究的目标是研究其特点和 主动式和被动式水和溶质跨河运输的调节 肺泡上皮屏障正常和异常。我们会研究 两种离体肺泡剂的转运特性 上皮组织。这些制剂将被用来确定运输 测量肺泡上皮运输的溶质和水的途径 在各种生理和病理条件下的特性，以及 确定肺上皮屏障的完整性在 肺泡性肺水肿的发病机制及消退机制。这个 这些研究的总体前提是关于 水和溶质跨海运移的特征及调控 肺泡上皮本身将导致进一步的洞察不仅是 这种组织的基本功能，也成了这样的重要性 肺泡液生成和排出过程中的传输特性。这个 调查将采取双管齐下的方法，利用收获的 哺乳动物肺泡上皮细胞的原代培养和中空肺 两栖动物。哺乳动物II型细胞的单层将被研究 多孔性和非多孔性表面，以及两栖动物肺将被研究为 囊和扁平的床单。被动输运特性的具体研究 这两种制剂中将包括被动的测定 非电解质通量(包括渗透率和反射率 系数)、静水压力和/或渗透压力引起的水通量 梯度，跨肺泡上皮运输的途径，以及 对温度和温度等物理化学参数传输的影响 PH值。主动运输研究将包括对生物电的测量 特性(包括自发电位差、组织电阻 和短路电流)、活性离子通量、由于 主动溶质转运以及某些激素和药物的作用 (例如，包括茶碱和ADH)。预计我们的 研究将提供有关以下方面的信息： 肺泡上皮细胞的主动和被动溶质及水转运 障碍。这些数据应该有助于我们了解哺乳动物的肺泡 正常肺和异常肺中的上皮运输特性及其 肺泡性肺炎的预防、形成和消退作用 活体内的水肿。

The goals of the proposed research are to study the characteristics and regulation of active and passive water and solute transport across the normal and abnormal pulmonary alveolar epithelial barrier. We will study the transport properties of two preparations of isolated alveolar epithelium. These preparations will be used to determine transport pathways of solutes and water, measure alveolar epithelial transport properties under various physiological and pathological conditions, and determine the role of the integrity of lung epithelial barriers on the mechanisms of pathogenesis and resolution of alveolar pulmonary edema. The overall premise of these studies is that information about the characteristics and regulation of the transport of water and solutes across alveolar epithelium per se will lead to further insight not only into the basic functions of this tissue, but also into the importance of such transport properties in the generation and removal of alveolar fluid. The investigations will follow the two-pronged approach of utilizing harvested mammalian alveolar epithelial cells in primary culture and the hollow lungs of amphibians. Monolayers of mammalian Type II cells will be studied on both porous and nonporous surfaces, and amphibian lungs will be studied as sacs and flat sheets. Specific studies of the passive transport properties of these two preparations will include determination of passive non-electrolyte fluxes (including permeabilities and reflection coefficients), water fluxes due to hydrostatic and/or osmotic pressure gradients, pathways for transport across alveolar epithelium, and the effects on transport of physicochemical parameters such as temperature and pH. Active transport studies will include measurements of bioelectric properties (including spontaneous potential differences, tissue resistance and short circuit current), active ion fluxes, water movements due to active solute transport, and the effects of certain hormones and drugs (including, for example, theophylline and ADH). It is anticipated that our studies will provide information on the characteristics and regulation of active and passive solute and water transport of the alveolar epithelial barrier. These data should help us understand mammalian alveolar epithelial transport properties, in normal and abnormal lungs, and their roles in the prevention, formation, and resolution of alveolar pulmonary edema in vivo.