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Interfacial Adsorption of Pulmonary Surfactant

$395,300R01FY2007HLNIH

Oregon Health & Science University, Portland OR

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Pulmonary surfactant lowers surface tension in the lungs. The type II pneumocyte synthesizes and secretes a mixture of lipids and proteins that together act as a surfactant, adsorbing to the air/water interface of the thin liquid layer that lines the alveoli and lowering surface tension. The function of pulmonary surfactant is essential for normal breathing. When surface tension is elevated, ventilation injures the lungs, damaging the thin barrier that separates alveolar air from capillary blood. The injury leads to pulmonary edema and respiratory failure. The best defined disorder caused by elevated surface tension is the Respiratory Distress Syndrome, in which premature infants are born prior to developing normal levels of surfactant. The most conclusive evidence that deficient surfactant causes the disorder is the improved survival that results from treating these infants with exogenous surfactant. The most effective of these agents, however, are obtained from animals, and these surfactant are unavailable in sufficient amounts for treating adults with other disorders related to abnormal surfactant. Our studies focus on the process by which surfactant vesicles adsorb to the interface. The absence of the hydrophobic surfactant proteins, which promote the rapid formation of the surfactant film, leads to RDS, despite normal levels of the surfactant lipids. These results demonstrate the fundamental importance of the process by which constituents adsorb to the interface. The mechanisms by which adsorption occurs is the focus of our studies. Relevance: Pulmonary surfactant forms a thin films that lines the small alveolar air sacks of the lungs. In the absence of these films, the process of ventilation injures the thin barrier between the alveolar air space and the capillary blood, leading to the flooding of the air spaces and respiratory failure. This research will determine how the surfactant films form to promote the basis for understanding why pulmonary diseases occur and how they can be treated. [unreadable] [unreadable] [unreadable]

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