The long-term goal of this project is to elucidate the control of surfactant secretion in the newborn. Such information is vital for the prevention and/or control of the respiratory distress syndrome (RDS) in premature human newborns.
The specific aims for the proposed period of funding are twofold. First, to elucidate the mechanism by which labor stimulates surfactant production in the newborn, to determine if this effect is influenced by the sex of the newborn and if the stimulatory effect of ventilation is mediated similarly.
The second aim i s to choose agents of potential physiological significance (i.e., from the studies in Aim #1) and study in detail their effects on surfactant secretion and/or synthesis in isolated type II cells. The respiratory distress syndrome of the newborn (RDS) is still a major cause of morbidity and mortality among premature infants. RDS is a developmental disorder due to immaturity of the lung with consequent insufficient surfactant. Many studies have focused on surfactant synthesis in the fetus and a variety of hormones and other agents have been shown to accelerate surfactant production in the fetal lung. Some of these are used clinically in the prevention of RDS. Surfactant production in the newborn has been less studied. Yet it is known that a number of postnatal factors influence surfactant production and the incidence of RDS. There is a lower incidence of RDS in infants delivered after labor than in its absence. Labor has been shown to stimulate surfactant production in animal studies. Birth and ventilation are also associated with increased surfactant production. Males are more prone to RDS than females suggesting a sex difference in surfactant production.
The aim of this project is to determine how some of these factors influence surfactant secretion. In this largely biochemical study we will use the following experimental approaches to measure various parameters of surfactant production: lung lavage phospholipid content and composition; rates of precursor incorporation into specific phospholipids in lung slices; activities of enzymes of lung phospholipid biosynthesis; rate of surfactant secretion in newborn lung slices; and synthesis and secretion of surfactant in isolated type II cells. In general, the approach is to make the initial physiological observation in the intact animal, define its mechanism in the in vitro lung systems and carry out more mechanistic studies in the type II cells.
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