Acute respiratory distress syndrome (ARDS) is a serious disorder with a mortality rate between 50-70%. It is characterized by intense inflammatory response. This response consists of an influx and sequestration of neutrophils into the lung with the release of noxious mediators such as neutrophil elastase. EIastase may cleave and destroy elastin as well as macromolecules such as surfactant apoproteins. Surprisingly, almost nothing is known about the functional relationship between surfactant dysfiinction and changes in elastin in ARDS during lung injury and repair. Whether the status ofelastin synthesis at the time of the injury or the presence of abnormaI clastin affect the overall response to lung injury is unknown. Furthermore, while phospholipids possess anti-inflammatory properties, it is unknown what effect exogenous would have on reducing the inflammatory response and the effect on elastin damage after lung injury. The overall goal of this proposal therefore is to analyze the role of surfactants in modulating elastin synthesis in a transgenic mouse model of acute lung injury, created by the intratracheal administration of bacterial endotoxin into transgenic mice harboring and actively expressing a number of different elastin gene mutations. New information from these studies may contribute to a better understanding of factors related to ARDS survival and recovery, with and without pulmonary sequelae. They may also contribute to a better understanding of the use of exogenous surfactant therapy in ARDS.
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