The respiratory distress syndrome of the newborn, which is due to immaturity of the fetal lungs at birth, remains a major cause of morbidity and mortality in the U.S. It is proposed to investigate mechanisms of fetal lung development at the cellular level and to develop markers for this process. The studies will be performed with cultures of differentiated type II cells from fetal rat lung and with recently developed cultures of hormone responsive undifferentiated fetal type II cells (pre-type II cells). In order to determine whether changes in specific cell surface proteins occur in association with characteristic intracellular changes during differentiation, the glycoproteins on the surface of differentiated and pre-type II cells which bind the Maclura pomifera lectin (MPA) will be isolated and compared. In addition, monoclonal antibodies will be developed to the MPA binding proteins of the differentiated type II cells and used to compare these cells to pre-type II cells and to pre-type II cells whose maturation has been induced in vitro. These specific antibodies will also provide valuable markers for isolating and identifying type II cells. It is currently not known whether mature fetal and adult type II cells are essentially the same. These cells will be compared by examining the functional characteristics or antigenicity of important intracellular and cell surface proteins. The question of whether glucocorticoids act directly on fetal type II cells or whether all steroid effects are fibroblast mediated will be addressed in the pre-type II cell model. Glucocorticoid induction of the following steroid inducible parameters will be studied in pre-type II cell cultures containing fibroblasts and in cultures from which the fibroblasts have been removed: Surfactant associated apoprotein (35 Kda) synthesis, DSPC and PG synthesis, fatty acid synthesis and cholinephosphate cytidylyltransferase and fatty acid synthetase activity. In those situations where glucocorticoids appear to be acting directly on the type II cell, further support for direct action will be sought by examining the receptor-response relationships.
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