These studies aim towards greater understanding of fetal and neonatal development and of maintenance, regeneration and restoration of mammalian tracheobronchial mucociliary epithelium (TBE). The hypotheses that mucous cells play a common and major role during fetal and neonatal development and during maintenance of the adult epithelium and regeneration of the same following injury, to produce and/or restore the mucociliary state, and that vitamin A levels regulate cell division and phenotypic expression of mucous cells, will be tested. The respective roles played by mucous cells and basal cells in regeneration of TBE will be characterized quantitatively in rat tracheas in vivo and human bronchus in vitro, using autoradiographic and stathmokinetic methods. The order of appearance of primordial specialized cells (basal, mucous, ciliated) will be defined in fetal trachea and the development of fetal and neonatal tracheal epithelium will be characterized quantitatively in hamsters using autoradiographic and stathmokinetic techniques. Furthermore, restoration of mucociliary epithelium following oral administration of vitamin A to hamsters previously deprived of the vitamin, will be defined quantitatively and the respective roles of mucous cells and basal cells in restoration of the mucociliary state will be defined. Ciliary activity removes particulates and mucus from the airways; cilia only function efficiently when bathed in mucus secretion. Diverse types of injury cause the formation of widespread metaplastic non-ciliated epithelium of epidermoid character which predisposes to infection. Increased knowledge regarding control of phenotypic expression of cells which constitute this epithelium has significance regarding the introduction of therapeutic measures to restore the mucociliary state following injury and promises to yield more complete understanding of the histogenesis of many bronchial diseases including bronchogenic carcinoma.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Pathology A Study Section (PTHA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
Schools of Medicine
United States
Zip Code
Sigler, R E; Jones, R T; Hebel, J R et al. (1987) Hamster tracheal organ culture in serum-free media: a quantitative comparison of in vitro epithelial morphology with that of in vivo controls. In Vitro Cell Dev Biol 23:100-10
McDowell, E M; Ben, T; Newkirk, C et al. (1987) Differentiation of tracheal mucociliary epithelium in primary cell culture recapitulates normal fetal development and regeneration following injury in hamsters. Am J Pathol 129:511-22
Otani, E M; Newkirk, C; McDowell, E M (1986) Development of hamster tracheal epithelium: IV. Cell proliferation and cytodifferentiation in the neonate. Anat Rec 214:183-92
Saffiotti, U; Stinson, S F; Keenan, K P et al. (1985) Tumor enhancement factors and mechanisms in the hamster respiratory tract carcinogenesis model. Carcinog Compr Surv 8:63-92
McDowell, E M; Keenan, K P; Trump, B F (1985) The pathogenesis of hormone-producing tumors of the lung. Recent Results Cancer Res 99:94-106
McDowell, E M; Newkirk, C; Coleman, B (1985) Development of hamster tracheal epithelium: I. A quantitative morphologic study in the fetus. Anat Rec 213:429-47
Coleman, B; McDowell, E M (1985) Development of hamster tracheal epithelium: III. Illustration of statistical methods for proportional data in biology. Anat Rec 213:457-63
McDowell, E M; Newkirk, C; Coleman, B (1985) Development of hamster tracheal epithelium: II. Cell proliferation in the fetus. Anat Rec 213:448-56
Strum, J M; Latham, P S; Schmidt, M L et al. (1985) Vitamin A deprivation in hamsters. Correlations between tracheal epithelial morphology and serum/tissue levels of vitamin A. Virchows Arch B Cell Pathol Incl Mol Pathol 50:43-57