LUNG EPITHELIAL TRANSPORT PROPERTIES AND ALVEOLAR EDEMA

肺上皮运输特性和肺泡水肿

• 批准号: 3354874
• 负责人: EDWARD DAVID CRANDALL
• 金额: $ 18.49万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354874
• 关键词: active transport; biological fluid transport; hormone regulation /control mechanism; ion transport; lung alveolus; lung disorder; passive transport; pulmonary edema; respiratory epithelium; scintillation spectrometry; solute; tissue /cell culture; vasopressins

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.

拟议研究的目标是研究特征和 调节主动和被动的水和溶质跨过 正常和异常的肺泡上皮屏障。 我们将学习 两种离体肺泡制剂的转运特性 上皮。 这些准备工作将用于确定运输 溶质和水的途径，测量肺泡上皮运输 在各种生理和病理条件下的特性，以及 确定肺上皮屏障完整性对 肺泡性肺水肿的发病机制和解决机制。 这 这些研究的总体前提是关于 水和溶质跨界运输的特征和调节 肺泡上皮本身不仅会导致人们进一步了解 该组织的基本功能，还包括此类的重要性 肺泡液产生和清除的运输特性。 这 调查将采用双管齐下的方法，利用所收获的 原代培养的哺乳动物肺泡上皮细胞和中空肺 两栖动物。 将研究哺乳动物 II 型细胞的单层 多孔和无孔表面以及两栖动物的肺将被研究为 囊和平板。 被动传输特性的具体研究 这两项准备工作将包括确定被动 非电解质通量（包括渗透率和反射率） 系数），静水压和/或渗透压引起的水通量 梯度，穿过肺泡上皮的运输途径，以及 温度等物理化学参数对运输的影响 酸碱度。 主动运输研究将包括生物电的测量 特性（包括自发电位差、组织电阻 和短路电流）、活性离子通量、水运动 活性溶质转运以及某些激素和药物的影响 (包括例如茶碱和抗利尿激素)。 预计我们的 研究将提供有关特征和监管的信息 肺泡上皮的主动和被动溶质和水运输 障碍。 这些数据应该有助于我们了解哺乳动物的肺泡 正常和异常肺中的上皮转运特性及其 肺泡性肺病的预防、形成和解决中的作用 体内水肿。