The pulmonary surfactant system is necessary for the maintenance of normal lung function. Recent evidence suggests that the inhibition of pulmonary surfactant biophysical activity by plasma proteins and other agents found in the alveolar region during lung injury may be important to the lung pathophysiology seen in both the adult and neonatal respiratory distress syndromes (ARDS and RDS, respectively). This project is designed to characterize potential mechanisms by which these exogenous agents inhibit the biophysical function of natural and artificial pulmonary surfactants. These goals will be achieved by taking advantage of differential sediment abilities of surfactant aggregates and proteins to determine the presence or absence of molecular interactions between the two in combination with physiologically relevant characterization of the surface activity of themixtures (including the use of an oscillating bubble surfactometer equipped with a hypophase exchange system available only in this laboratory). In addition, more complex experiments utilizing preformed protein or surfactant surface films will be carried out to determine to what extent plasma proteins are able to block the entry of surfactant molecules into the surface film. These experiments will give information into the mechanisms by which proteins are able to inhibit surfactant biophysical function that may be extremely useful in future surfactant therapy in lung disease states.
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