TISSUE CULTURE AND RESPIRATORY EPITHELIAL FUNCTION

最近的研究表明，囊性纤维化患者的呼吸道分泌物增厚 可能是由于呼吸道离子和水运输的异常所致 上皮组织。已检测到CF上皮功能异常 从鼻子、气管和大支气管。然而，已经进行了彻底的研究 受限于组织可获得性。目前还没有关于离子输运功能的研究 有正常肺或CF肺的远端小气道可用。这个项目 将开发和评估组织培养模型，以允许 单分子膜离子传输和溶质渗透性的表征 来自近端和最终远端呼吸道的上皮细胞。两种模式 将发展：(1)生长在薄胶原膜上的细胞，(2)细胞 重新填充裸露的兔气管。后一种模型提供了一个 细胞生长的间充质表面，允许正常形态 差异化。在这些模型中对近端呼吸道细胞的研究将 允许将培养的细胞与体内或摘除的研究进行比较 组织，以评估模型。组织培养将提供足够的 用于更彻底地描述肺内缺陷的材料 区域。随后，从兔、正常人的远端呼吸道提取的细胞， 并对慢性萎缩性胃炎患者进行评估。离子输运的定义 近端和远端呼吸道上皮的特性将促进 对CF正常生理功能和病理生理学的认识 肺部疾病。CF有效治疗的新途径可能从 这些信息。

Recent studies suggest that thickened airway secretions in cystic fibrosis may result from abnormalities of ion and water transport by the airway epithelium. Functional abnormalities have been detected in CF epithelium from nose, trachea, and large bronchi. However, thorough studies have been limited by tissue availability. No studies of ion transport function in distal, small airways of normal or CF lungs are available. This project will develop and evaluate tissue culture models which permit characterization of ion transport and solute permeability by monolayers of epithelial cells from proximal and ultimately distal airways. Two models will be developed: (1) cells grown on thin collagen membranes, (2) cells repopulating a denuded rabbit trachea. The latter model provides a mesenchymal surface for cell growth, which permits normal morphologic diffentiation. Studies of proximal airway cells in these models will permit comparison of the cultured cells with studies of in vivo or excised tissue, to evaluate the models. Tissue culture will provide sufficient material for a more thorough characterization of the defects in this lung region. Subsequently, cells from distal airways of rabbits, normal humans, and CF patients will be evaluated. Definition of the ion transport properties of proximal and distal airway epithelium will promote understanding of normal physiologic function and the pathophysiology of CF lung disease. New approaches to effective therapy of CF may develop from this information.