POSTNATAL DEVELOPMENT OF BRONCHIOLOAR EPITHELIUM

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Our long range goal is to perform experiments that will increase our understanding of the perinatal (mainly postnatal) maturation of the epithelium of small conducting airways (bronchioles) of the lung. This goal is an outgrowth of our long standing interest in the bronchiolar Clara cell. We have chosen to explore the postnatal development of the epithelium of bronchioles because 1) our preliminary findings indicate that in rats the maturation of this epithelium is in great part an early postnatal event, 2) because knowledge of the maturation of Clara cells and of the attainment of the adult composition of bronchiolar epithelium and the regulation of these developmental processes is virtually nonexistant and, 3) because these airways are sites of major diseases in infants and adults. Our more specific aims are to attempt to determine which factor(s) signals the initiation of maturation of Clara cells (as determined by a fall in their glycogen content and an increase in the volume fraction of their secretory granules and rough endoplasmic reticulum) and to determine if there is a "critical period" for the maturation of cells in bronchioles. We hope to achieve our specific aims using light and transmission electron microscopy, morphometry and knowledge of the developing lung. We think we can achieve our goals because we have experience with many of the procedures we plan to use and because the proposed studies have a firm and rational base in our preliminary work. The proposed study should provide information about an area little studied, and may provide insight into risk factors for the development of chronic obstructive lung disease in children and adults and may eventually be applied to improve the health care of neonates.