LUNG EPITHELIAL TRANSPORT PROPERTIES AND ALVEOLAR EDEMA

肺上皮运输特性和肺泡水肿

• 批准号: 3486189
• 负责人: EDWARD DAVID CRANDALL
• 金额: $ 26.39万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 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 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3486189
• 关键词: Rana; active transport; biological fluid transport; hormone regulation /control mechanism; ion transport; laboratory rat; lung alveolus; lung injury; 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 pulmonary alveolar epithelial barrier, and to understand their roles in alveolar homeostasis and edemagenesis. We will study these transport properties using two preparations of isolated alveolar epithelium, in addition to the intact epithelium of the perfused rat lung. The overall premise of our program is that information about the characteristics and regulation of the transport of water and solutes across alveolar epithelium will lead to further insight not only into the basic functions of this tissue barrier, but also into the importance of such transport properties in the generation and removal of alveolar fluid under normal and abnormal conditions. The investigations will follow a multi-pronged approach of utilizing the two isolated epithelial preparations (mammalian alveolar epithelial cells in primary culture, and the hollow lungs of amphibians) to generate fundamental information about transport across the alveolar epithelial barrier. Mammalian type Ii cells will be studied primarily as monolayers n porous surfaces, and amphibian lungs will be studied as sacs and flat sheets. Information generated in these basic investigations will be compared to that from studies of transport across the intact alveolar epithelium of the perfused mammalian lung. Specific studies of the passive transport properties of these preparations will include determination of passive solute permeabilities, water flux due to hydrostatic and/or osmotic pressure gradients, and pathways for transport across the alveolar epithelium. Active transport studies will include measurements of bioelectric properties (including spontaneous potential difference, tissue resistance and short circuit current), active ion (sodium) fluxes, and water movements due to active solute transport. Investigation of the effects of physiocochemical parameters (e.g., temperature, pH), pharmacological agents (e.g., hormones), and especially lung injury (e.g., by oxidants) constitute a major part of this proposal. It is anticipated that our investigations will provide further insight into the transport characteristics of the alveolar epithelial barrier in normal and abnormal adult mammalian lungs, and into the roles of these barrier properties in normal alveolar homeostasis and alveolar pulmonary edema in vivo.

拟议研究的目标是研究 主动和被动水的特性和调节， 溶质转运穿过肺泡上皮屏障， 了解它们在肺泡内环境稳定中的作用， 水肿 我们将使用两个 分离的肺泡上皮的制备，除了 灌注大鼠肺的完整上皮。 总的前提是 我们的计划是，有关特征的信息， 调节水和溶质通过肺泡的运输 上皮细胞将导致进一步的了解，不仅是基本的 这种组织屏障的功能，也体现了其重要性 在产生和去除的这种传输特性 正常和异常情况下的肺泡液。 的 调查将采取多管齐下的方法， 两种分离的上皮制备物（哺乳动物肺泡 原代培养的上皮细胞，以及 两栖动物），以生成有关运输的基本信息 穿过肺泡上皮屏障 哺乳动物II型细胞 将主要作为多孔表面上的单层进行研究， 两栖动物的肺将被研究为囊和平板。 这些基本调查产生的信息将 相比之下，从运输的研究，在完整的 灌注的哺乳动物肺的肺泡上皮。 具体 这些制剂的被动输运性质的研究 将包括测定被动溶质渗透率、水 由于流体静压和/或渗透压梯度引起的通量，和 通过肺泡上皮细胞的运输途径。 活性 运输研究将包括测量生物电 特性（包括自发电位差、组织 电阻和短路电流），活性离子（钠）通量， 以及由于主动溶质运输引起的水运动。 研究生理化学参数的影响（例如， 温度，pH），药理学试剂（例如，激素），以及 尤其是肺损伤（例如，氧化剂）构成的主要部分 这个提议。 预计我们的调查将提供 进一步了解肺泡的运输特性 正常和异常成年哺乳动物肺中的上皮屏障， 以及这些屏障特性在正常肺泡中的作用 体内稳态和肺泡肺水肿。