The alveoli of the lung are lined with pulmonary surfactant, a lipid-rich material that lowers the surface-tension within the alveoli and there by prevents aveolar collapse. The ability of pulmonary surfactant to reduce the surface tension at end expiration is of critical importance at birth. A deficiency of pulmonary surfactant is considered to be responsible for Respiratory Distress Syndrome (RDS). RDS occurs almost exclusively in premature infants and is a major cause of neonatal death. At the end of gestation lung maturation, especially the onset of surfactant production is regulated by endogenous fetal glucocorticoids. Evidence is presented that the glucocorticoid effect on lung maturation is dependent on mesenchymal epithelial interactions. In response to glucocorticoids, the lung mesenchyme produces an oligopeptide, fibroblast pneumonocyte factor (FPF) which in turn stiumlates the formation of surfactant by alveolar Type II cells. Our goal is to determine by which mechanism FPF regulates surfactant snythesis in alveolar Type II cells from fetal lung. Initial studies will explore the effect of FPF on key enzymes involved in the synthesis de novo of surfactant associated phosphatidylcholine. We have recently identified cholinephosphate cytidylyltransferase to be the enzyme catalyzing the rate-limiting reaction in the formation of phosphatidylcholine by alveolar Type II cells. Further evaluation will include the regulatory mechanism(s) (e.g. phosphorylation-dephosphorylation, translocation) of this enzyme and its modulation, if present, by FPF. These studies should provide a better understanding in the mechanism by which lung maturation is regulated.
