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Author Notes:

Tel.: 404-727-4769; Fax: 404-727-3236; E-mail: tgauthi@emory.edu

FAEE analysis was performed by the Children's + Emory Biomarkers Core.

Subjects:

Research Funding:

NIH NIAAA. Grant Numbers: F32AA019880-01, R01 AA013979

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Substance Abuse
  • Alveolar Macrophage
  • Fetal Alcohol
  • Fatty Acid Ethyl Esters
  • Mitochondria
  • Reactive Oxygen Species
  • UTERO ETHANOL EXPOSURE
  • PRENATAL ALCOHOL EXPOSURE
  • GLUTATHIONE AVAILABILITY
  • GUINEA-PIG
  • MONONUCLEAR-CELLS
  • EPITHELIAL-CELLS
  • FED RATS
  • LUNG
  • DYSFUNCTION
  • METABOLISM

Fatty Acid Ethyl Esters Disrupt Neonatal Alveolar Macrophage Mitochondria and Derange Cellular Functioning

Tools:

Journal Title:

Alcoholism: Clinical and Experimental Research

Volume:

Volume 39, Number 3

Publisher:

, Pages 434-444

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Chronic alcohol exposure alters the function of alveolar macrophages (AM), impairing immune defenses in both adult and neonatal lungs. Fatty acid ethyl esters (FAEEs) are biological markers of prenatal alcohol exposure in newborns. FAEEs contribute to alcohol-induced mitochondrial (MT) damage in multiple organs. We hypothesized that in utero ethanol exposure would increase FAEEs in the neonatal lung and that direct exposure of neonatal AM to FAEEs would contribute to MT injury and cellular dysfunction. Methods: FAEEs were measured in neonatal guinea pig lungs after ± in utero ethanol exposure via gas chromatography/mass spectrometry. The NR8383 cell line and freshly isolated neonatal guinea pig AM were exposed to ethyl oleate (EO) in vitro. MT membrane potential, MT reactive oxygen species generation (mROS), phagocytosis, and apoptosis were evaluated after exposure to EO ± the MT-specific antioxidant mito-TEMPO (mitoT) or ± the pan-caspase inhibitor Z-VAD-FMK. Whole lung FAEEs were compared using the Mann-Whitney U-test. Cellular results were analyzed using 1-way analysis of variance, followed by the Student-Newman-Keuls Method for post hoc comparisons. Results: In utero ethanol significantly increased ethyl linoleate and the combinations of ethyl oleate + linoleate + linolenate (OLL), and OLL + stearate in the neonatal lung. In vitro EO caused significant MT dysfunction in both NR8383 and primary neonatal AM, as indicated by increased mROS and loss of MT membrane potential. Impaired phagocytosis and apoptosis were significantly increased in both the cell line and primary AM after EO exposure. MitoT conferred significant but only partial protection against EO-induced MT injury, as did caspase inhibition with Z-VAD-FMK. Conclusions: In utero ethanol exposure increased FAEEs in the neonatal guinea pig lung. Direct exposure to the FAEE EO significantly contributed to AM dysfunction, in part via oxidant injury to the MT and in part via secondary apoptosis.

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© 2015 The Authors. Alcoholism: Clinical and Experimental Research published by Wiley Periodicals, Inc. on behalf of Research Society on Alcoholism.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits distribution, public display, and publicly performance, making multiple copies, distribution of derivative works, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.

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