TISSUE CULTURE AND RESPIRATORY EPITHELIAL FUNCTION

点击翻译按钮获取中文摘要

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.