The goal of this project has been to define the pattern of epithelial maturation in the tracheobronchial airways of primate lung. Cell-to-cell and matrix-to-cell interactions have been emphasized. Because of the pivotal role of mucous goblet cells in two major upper respiratory diseases of man, cystic fibrosis and chronic bronchitis, we have narrowed the scope of this proposal to focus on: a) the differentiation of mucous cells and their biosynthetic capacity and b) the relationship of mesenchymal elements to the differentiation process. Three hypotheses will be tested: a) mucous goblet cells differentiate in utero by producing first a neutral, then on acid, and finally a sulfated glycoprotein; b) mucous goblet cell glycoconjugate composition differs in the fetus, newborn, young and adult animal; and c) composition of the adjacent mesenchymal matrix and basal lamina influences secretory cell differentiation. Using the lung tissue of 49 fetal and 12 postnatal rhesus collected in years 01 and 02 of this project, we will characterize the change in glycoconjugates of surface and glandular secretory cells during development by light and electron microscopic cytochemistry. With a panel of 12 monoclonal antibodies raised against adult rhesus tracheal mucus, we will delineate the change in expression of glycoprotein antigens during development. To test biosynthetic capability of differentiating mucous cells, fetuses and newborns will be injected with rabiolabeled glycoprotein precursors and uptake will be assessed autoradiographically. The differentiation pattern in respiratory bronchioles will be used to assess the effect basal lamina and matrix components have on secretory cell maturation. We have concluded from the first 25 months of this project that: a) respiratory bronchioles of adult rhesus monkeys are lined by three distinct epithelial populations whose distribution depends on proximity to the pulmonary artery; b) tracheal epithelial differentiation begins during the first trimester of pregnancy and is nearly complete by birth; c) the sequence of appearance of adult cell types is ciliated, mucons, basal and small mucous granule; d) epithelial maturation differs between the cartilaginous and memoranous trachea; e) mucous cell differentiation is a three-phase process, beginning early in gestation and continuing through the postnatal periods; f) the three populations in respiratory bronchioles differentiate at different rates depending on proximity to the pulmonary artery.
Showing the most recent 10 out of 16 publications
