REGIONAL ION TRANSPORT ACROSS AIRWAY EPITHELIUM

跨气道上皮的区域离子传输

• 批准号: 2378773
• 负责人: STEPHEN T BALLARD
• 金额: $ 10.16万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2378773
• 关键词: amiloride; biological fluid transport; bronchioles; bumetanide; cystic fibrosis; electrical conductance; hydrostatic pressure; ion transport; isolation perfusion; pulmonary edema; radiotracer; respiratory epithelium; sodium potassium exchanging ATPase; swine

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.

关于肺液平衡的传统理论长期以来一直接受这一概念 远端小气道上皮向气道腔内分泌液体 来补充呼吸道表面的水分，支持粘液纤毛的运输。因为这就是 腔内液体被纤毛扫入大的呼吸道，在那里聚集 横截面积要小得多，据推测，液体 必须进行吸收以减少液体体积并防止堵塞 空域。主动的跨上皮离子转运被认为提供了 这种液体通过呼吸道上皮细胞运动的主要驱动力。 这些关于呼吸道液体平衡的理论得到了以下发现的支持 积极接触大型呼吸道，如气管和大支气管 吸收离子(由主动的Na+吸收驱动)。然而，该地区 出现离子和液体分泌的小气道仍然难以捉摸 因为肺的复杂形态排除了对这些的研究 用常规方法提取组织。最近，通过以下方式开发了技术 这个实验室允许对小支气管进行解剖和插管 和细支气管(管腔直径100微米)，以便离子传输和 生物电学特性现在可以在体外评估大型和 小气道上皮。本研究的中心假设是 在跨上皮离子和液体运输方面存在差异 大、小气道上皮。具体地说，假设 离子和液体通过大的呼吸道上皮和分泌物被吸收 穿过小气道上皮。这些假说将在三个方面进行检验 阶段：L)跨上皮生物电学特性的表征，2) 测量生理上重要的溶质的放射性同位素通量， (3)跨上皮液流量的测定。大型航空公司将成为 安装在Ussing室中，而中到小型通道将 用玻璃管或聚乙烯管灌装。选择性抑制剂和 钠和氯运输的刺激物将被用来识别 这些特定的途径和调节跨上皮离子和液体 流。活性离子输运的鉴定与表征 存在于呼吸道上皮特定区域的突起 将极大地促进我们对病原学和 重要的肺部疾病和紊乱的病理生理学 囊性纤维化和肺水肿。