Surface liquids and cilia work in concert (mucociliary clearance) to protect the large airways from injury. Development of these critical components of tracheobronchial epithelial function has not been evaluated systematically or comprehensively. Furthermore, little is known about the short or long term effects of injury to immature airways on mucociliary clearance and subsequent health of the lung. We propose to employ coordinated ultrastructural, physiological, and biochemical techniques to describe ion transport, secretory and ciliary/mucociliary mechanisms in developing ferret airways. In addition, we will infect young ferrets with influenza A virus and use this model of injury to large airway epithelium to delineate extent and duration of effects on mucociliary function. Sampling healthy and virus-infected tracheas at intervals from birth to maturity, we will: 1) describe morphologic features of surface epithelium and glands which relate to mucociliary function, including relative numbers of goblet cells in surface epithelium, ciliary structure especially as it relates ciliogenesis, junctional complexes, and cell turnover (in the injured epithelium), 2) estimate in vitro ciliary beat frequency, 3) assess electrical and transport properties of epithelium, 4) assess biosynthesis, composition/structure, and modulation of secretion of mucins, and 5) measure the rate of tracheal mucus transport in vivo. We anticipate that differences in structure, ion transport and/or secretory products will be documented early in life, as compared with mature animals, and that these differences may be reflected in altered mucus transport rates. We further predict that orderly developmental changes will be disturbed by epithelial injury soon after birth. It is our hypothesis that injury to airways epithelium before or during points of functional transition will have more severe or prolonged consequences than later injury. The integrated, multidisciplinary studies of healthy and injured airways proposed here will permit a systematic test of these predictions and should provide baseline data which will facilitate future studies of mucociliary function at other levels in the airways and in human subjects.
| Voter, K Z; Leigh, M W; Boat, T F et al. (1992) Development of mucociliary transport in the postnatal ferret trachea. J Appl Physiol 73:1500-3 |
| Carson, J L; Collier, A M; Gambling, T M et al. (1988) Development, organization, and function of tight junctional complexes in the tracheal epithelium of infant ferrets. Am Rev Respir Dis 138:666-74 |
| Curtis, L N; Carson, J L; Collier, A M et al. (1987) Features of developing ferret tracheal epithelium: ultrastructural observations of in vivo and in vitro differentiation of ciliated cells. Exp Lung Res 13:223-40 |
| Leigh, M W; Cheng, P W; Carson, J L et al. (1986) Developmental changes in glycoconjugate secretion by ferret tracheas. Am Rev Respir Dis 134:784-90 |
| Leigh, M W; Gambling, T M; Carson, J L et al. (1986) Postnatal development of tracheal surface epithelium and submucosal glands in the ferret. Exp Lung Res 10:153-69 |
