ALVEOLAR EPITHELIAL-CELL KERATIN EXPRESSION DURING LUNG DEVELOPMENT

Defining the expression and organization of keratins has provided insight into epithelial cell differentiation during tissue development and remodeling. We have used monoclonal antibodies to examine keratin distribution in lung epithelial cells in the rat from the preglandular phase of gestation to the adult. Of particular interest were the distributions of keratin No. 18 and keratin No. 19, since previous results have suggested these keratins may be important in alveolar epithelial cell transitions occurring in adult remodeling lung and in cultured type II cells. The epithelial tubes at 15 days of gestation do not react with 24A3 monoclonal antibody to keratin No. 18, nor is this antigen apparent by gel or immunoblot analysis. Staining is apparent at day 16, however, showing a light punctate pattern at the basal edge of the cells, and becomes prominent by day 17, with intensity greatest in the larger airway tubes. The intensity and number of cells in the parenchyma staining with 24A3 peaks at postnatal days 5 to 10, when proliferation and cytodifferentiation of type I and type II cells is most active. In the adult, staining of type II cells is present mainly at the cell periphery, and occasional reactive attenuated type I-like cells can be observed. Keratin No. 19 immunoreactivity is not present in the primitive epithelial tube until 19 days' gestation but predominantly stains type II pneumocytes in the adult rat lung throughout the entire cell. AE3 antibody to basic keratins stains similarly to keratin No. 19. We conclude that keratin No. 18 is expressed at high levels in type II cells during development in periods of intense proliferation and alveolarization. This correlates with our previous observations on keratin expression following bleomycin lung injury.