REGIONAL ION TRANSPORT ACROSS AIRWAY EPITHELIUM

肺液体平衡的传统理论长期以来一直认为 远端小气道上皮细胞分泌液体进入气道腔 以水合气道表面并支持粘膜纤毛运输。因为这 纤毛将内腔液体扫入大气道，在那里聚集 横截面积小得多，这是因为液体 必须发生吸收以减少液体体积并防止阻塞 领空并主动跨上皮离子转运被认为提供了 这是液体穿过气道上皮的主要驱动力。 这些关于气道液体平衡的理论得到以下发现的支持， 可进入的大气道，如气管和大支气管，积极地 吸收离子（由活性Na+吸收驱动）。然而，该地区 分泌离子和液体的小气道仍然难以捉摸 因为肺的复杂形态排除了这些研究， 用传统的方法。最近，已经开发了技术， 该实验室允许对小支气管进行解剖和插管 和细支气管（> 100 μ m管腔直径）， 现在可以在体外评估生物电特性， 小气道上皮。本研究的中心假设是 在跨上皮离子和液体转运方面存在差异， 大、小气道上皮。具体而言，假设 离子和液体通过大气道上皮吸收， 穿过小气道上皮。这些假设将在三个测试 阶段：1）跨上皮生物电特性的表征，2） 测量生理上重要的溶质的放射性同位素通量， 和3）测定跨上皮液体流量。大型航空公司将在 安装在Ussing室中，而中间到小气道将 用玻璃或聚乙烯管插入。选择性抑制剂和 钠和氯转运的刺激物将用于识别 这些特定的途径，并调节跨上皮离子和液体 流活性离子转运的鉴定和表征 存在于气道上皮细胞特定区域的突起 将极大地促进我们对病因学的理解， 重要肺部疾病和病症的病理生理学，例如 囊性纤维化和肺水肿

Conventional theories on lung liquid balance have long embraced the notion that distal small airway epithelium secretes liquid into the airway lumen to hydrate airway surfaces and support mucociliary transport. As this lumenal liquid is swept by cilia into the large airways, where aggregate cross sectional area is much smaller, it is reasoned that liquid absorption must occur to reduce liquid volume and prevent occlusion of the airspace. Active transepithelial ion transport is thought to provide the principal driving force for this liquid movement across airway epithelia. These theories on airway liquid balance are supported by findings that accessible large airways, such as trachea and large bronchi, actively absorb ions (driven by active Na+ absorption). However, the region of the small airways where secretion of ions and liquid occur remains elusive because the complex morphology of the lung precludes study of these tissues by conventional means. Recently, techniques have been developed by this laboratory which permit dissection and cannulation of small bronchi and bronchioles (> 100 mu m lumen diameter) so that ion transport and bioelectric properties can now be assessed in vitro in both large and small airway epithelium. The central hypothesis of the present study is that differences in transepithelial ion and liquid transport exist between large and small airway epithelium. Specifically, it is hypothesized that ions and liquid are absorbed across large airway epithelium and secrets across small airway epithelium. These hypotheses will be tested in three stages: l) characterization of transepithelial bioelectric properties, 2) measurement of radioisotopic fluxes of physiologically important solutes, and 3) determination of transepithelial liquid flow. Large airways will be mounted in Ussing chambers while intermediate to small airways will be cannulated with glass or polyethylene tubing. Selective inhibitors and stimulators of sodium and chloride transport will be used to identify these specific pathways and to modulate transepithelial ion and liquid flow. Identification and characterization of active ion transport processes which are present in specific regions of the airway epithelium will greatly facilitate our understanding of the etiology and pathophysiology of important pulmonary diseases and disorders such as cystic fibrosis and pulmonary edema.