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Biomed Res Int. 2014;2014:371593. doi: 10.1155/2014/371593. Epub 2014 Feb 19.

Alcohol induced mitochondrial oxidative stress and alveolar macrophage dysfunction.

Author information

1
Department of Pediatrics, Emory University, Atlanta, GA 30322, USA ; Children's Healthcare of Atlanta Center for Developmental Lung Biology, Atlanta, GA 30322, USA ; Division of Pulmonary, Allergy & Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
2
Department of Pediatrics, Emory University, Atlanta, GA 30322, USA ; Children's Healthcare of Atlanta Center for Developmental Lung Biology, Atlanta, GA 30322, USA.
3
Department of Pediatrics, Emory University, Atlanta, GA 30322, USA ; Children's Healthcare of Atlanta Center for Developmental Lung Biology, Atlanta, GA 30322, USA ; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University, 2015 Uppergate Drive, Atlanta, GA 30322, USA.

Abstract

An alcohol use disorder increases the risk of invasive and antimicrobial resistant community-acquired pneumonia and tuberculosis. Since the alveolar macrophage (AM) orchestrates the immune response in the alveolar space, understanding the underlying mechanisms by which alcohol suppresses AM phagocytosis is critical to improving clinical outcomes. In the alveolar space, chronic alcohol ingestion causes severe oxidative stress and depletes antioxidants which are critical for AM function. The mitochondrion is important in maintaining cellular redox balance and providing the ATP critical for phagocytosis. The focus of this study was to understand how alcohol triggers mitochondrial reactive oxygen species (ROS), stimulates cellular oxidative stress, and induces AM dysfunction. The current study also investigated the capacity of the mitochondrial targeted antioxidant, mitoTEMPOL (mitoT), in modulating mitochondrial oxidative stress, and AM dysfunction. Using in vitro ethanol exposure and AMs from ethanol-fed mice, ethanol promoted mitochondrial dysfunction including increased mitochondrial ROS, decreased mitochondrial membrane potential, and decreased ATP. Treatment with mitoT reversed these effects. Ethanol-induced decreases in phagocytosis and cell viability were also attenuated with mitoT. Therefore, antioxidants targeted to the mitochondria have the potential to ameliorate ethanol-induced mitochondrial oxidative stress and subsequent decreases in AM phagocytosis and cell viability.

PMID:
24701574
PMCID:
PMC3950485
DOI:
10.1155/2014/371593
[Indexed for MEDLINE]
Free PMC Article

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