Mucociliary clearance of inhaled particles from the tracheobronchial tree is an important defense mechanism of the lung. A failure of this clearance mechanism in disease probably results in retained mucous secretions and a predisposition to pulmonary infection. Circumstantial evidence indicates that airway secretion of ions, water, and mucus is an important factor in determining the rate of mucociliary clearance. Because the normal and abnormal physiology of these important secretory processes is only partially known, my proposal is to study the interrelationships among them. Prior investigation during the tenure of this proposal, showed that there is a predominant active movement of chloride directed toward the dog tracheal lumen and a lesser active Na+ movement in the opposite direction. Also, we obtained data that is consistent with Na-coupled electrogenic Cl-secretion in this epithelium. Further, we have begun to characterize the kinetics of mucous glycoprotein secretion by dog trachea using radioactive markers. All of these prior studies have employed intact tracheal tissue, in vitro. The use of intact tissue to study the physiology of airway secretion has certain inherent limitations related to cellular complexity of the tracheal epithelium, which renders it difficult to determine the functional contribution of individual cell types. In preliminary studies, we have developed a method in cats to isolate submucosal gland cells from the surface tracheal epithelium. In the proposed studies, we plan to refine our efforts and to isolate individual viable serous and mucous cells from the cat trachea. We plan to grow cells in monolayers in order to characterize the electrical and ion transport properties of the cells employing Ussing's short-circuit technique. Finally, we will employ several methods to characterize biochemically the macromolecular secretory products and responses of these cells.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL021314-08
Application #
3336458
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1977-07-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Culp, D J; Lee, D K; Penney, D P et al. (1992) Cat tracheal gland cells in primary culture. Am J Physiol 263:L264-75
Culp, D J; McBride, R K; Graham, L A et al. (1990) Alpha-adrenergic regulation of secretion by tracheal glands. Am J Physiol 259:L198-205
Marin, M G (1986) Pharmacology of airway secretion. Pharmacol Rev 38:273-89
Marin, M G; Culp, D J (1986) Isolation and culture of submucosal gland cells. Clin Chest Med 7:239-45
Culp, D J; Marin, M G (1986) Characterization of muscarinic cholinergic receptors in cat tracheal gland cells. J Appl Physiol 61:1375-82