In recent years our group has shown increasing evidence that chronic alcohol abuse has detrimental effects on lung function; in particular, exacerbation of acute respiratory distress syndrome (ARDS) and increased oxidative stress. In addition, alcohol abusers have an increased mortality when admitted to the hospital with community acquired pneumonia. We question what the underlying pathology of impaired bacterial clearance is that can ultimately lead to death in chronic alcoholics. During bacterial pneumonia, neutrophils are recruited to the alveolar space to phagocytize the infectious particles. Upon phagocytosis, neutrophils undergo apoptosis in order to kill the bacteria. In healthy individuals, macrophage phagocytize the apoptotic neutrophils. In previous studies, we have observed a reduction in macrophage phagocytosis in chronic ethanol-fed animals. We believe this resulting increase in apoptotic neutrophils in the alveolar compartment could be a contributing factor to ARDS and the increased mortality in chronic alcoholics with bacterial pneumonia. In this proposal we will attempt to elucidate the mechanisms of pulmonary neutrophil recruitment and transendothelial migration by examining rolling, adhesion, and migration of neutrophils in real-time using a well-established chronic ethanol model. In addition, we will investigate the effects of Klebsiella pneumoniae infection on neutrophil-endothelial cell interactions. Finally, we will test antioxidant rescue therapies via dietary supplementation with glutathione, N-acetylcysteine, and S-adenosylmethionine. These groups of experiments will provide insight into neutrophil-microvascular endothelial cell interactions and possible therapeutic treatments for chronic alcoholics with community acquired pneumonia. ? ? ?
| Tang, Sonja M; Gabelaia, Levan; Gauthier, Theresa W et al. (2009) N-acetylcysteine improves group B streptococcus clearance in a rat model of chronic ethanol ingestion. Alcohol Clin Exp Res 33:1197-201 |
