Excessive airway secretions are a common feature of several airway diseases including asthma, bronchitis and cystic fibrosis. These secretions are a complex mixture of mucous glycoproteins, electrolytes and water. One objective of the proposed research is to determine how epithelial ion transport is pathophysiologically regulated by the inflammatory mediators. This will be accomplished by mounting canine tracheal epithelium in vitro and measuring the electrical properties and radioactive ion fluxes before and during the administration of specific inflammatory mediators. Substances to be tested include bradykinin, prostaglandins, leukotrienes and other arachidonic acid metabolites. These mediators can be generated by more than one cell type, making cell-to-cell interactions of some importance. We therefore intend also to study how mediators released from other respiratory cells, canine mast cells and polymorphonuclear leukocytes, may also influence ion transport. The utilization of cultured cells derived from airway epithelial and mastocytoma cells will improve these studies in that purity and viability of each cell can be assured. These studies will be followed up by studies of the electrical properties of the epithelium in vivo. Mucus hypersecretion is histologically correlated with hypertrophy of the submucosal mucous glands and hyperplasia of the surface mucous cell or goblet cell. Several scientific techniques exist to study the regulatory physiology of the submucosal gland, but techniques have not been developed to study goblet cells. Another objective is to develop methods to study the regulation of goblet cells. An in vitro method to isolate goblet cells from other epithelial cells will be employed to study mucus secretion by primary cell culture. These studies will be followed up by an in vivo method, in which macromolecules will be labeled by injection of sodium 35sulfate. Both methods should supply enough time for equilibrium labeling to be achieved while protecting the tissue from the types of degeneration that occur in tissue explants. These techniques will enable the study of the role of autonomic agonists and inflammatory mediators in the initiation of mucus secretion.
