Chronic ethanol exposure sensitizes the lung in a mouse model of endotoxemia-induced acute lung injury : potential role of plasminogen activator inhibitor-1.

Abstract

Poole, Lauren G., "Chronic ethanol exposure sensitizes the lung in a mouse model of endotoxemia-induced acute lung injury : potential role of plasminogen activator inhibitor-1." (2015). The goal of this project is to characterize a new mouse model of alcoholenhanced acute lung injury (ALI) and to determine the role of plasminogen activator inhibitor-1 (PAI-1) in this model. Male mice (WT and PAI-1 -/-) were exposed to ethanol-containing Lieber-DeCarli diet or pair-fed control diet for 6 weeks; some animals were administered intraperitoneal lipopolysaccharide (LPS) prior to sacrifice. Chronic alcohol feeding enhanced induction of the chemokines MIP-2 and KC (murine IL-8 homologues) after LPS injection in wild type animals.This enhanced chemokine expression did not correlate with enhanced pulmonary neutrophil infiltration, however animals exposed to chronic ethanol showed sustained alveolar septal thickening and enhanced 4-HNE staining, indicative of inflammatory damage. Septal thickening was completely attenuated in PAI-1 -/-animals. This work has developed a new mouse model which can be used to vii elucidate the mechanisms of alcohol-enhanced ALI. A potential role of PAI-1 in alcohol-enhanced ALI has also been identified.viii