Sheena D Brown1, Lou Ann S Brown. 1. Department of Pediatrics, Emory University, and Center for Developmental Lung Biology, Children's Healthcare of Atlanta, Georgia 30322, USA.
Abstract
BACKGROUND: Previous studies have shown that chronic ethanol (EtOH) ingestion results in impaired alveolar macrophage function, increased TGF-β(1) production, and decreased antioxidant availability. Similarly, alternative activation (M2 activation) of alveolar macrophages also induces TGF-β(1) production and impairs macrophage function. However, the potential links between EtOH-induced alveolar macrophage derangements, M2 activation, TGF-β(1) production signaling, and oxidant stress have yet to be examined. We hypothesized that EtOH-induced oxidant stress and induction of TGF-β(1) signaling result in alternative activation which subsequently impairs the phagocytic capacity of alveolar macrophages. METHODS: Primary rat alveolar macrophages and the alveolar macrophages cell line NR8383 were treated with 0.08% EtOH ± the antioxidant glutathione (GSH) or a TGF-β(1) neutralizing antibody for 5 days. Outcome measures included TGF-β(1) production, reactive oxygen species (ROS) production, phagocytic capacity, and expression of markers of M2 activation. RESULTS: Chronic EtOH treatment greatly decreased alveolar macrophage phagocytic function, increased ROS production, increased TGF-β(1) , and increased expression of markers of M2 activation. GSH supplementation and inhibition of TGF-β(1) signaling during EtOH treatment prevented these alterations. CONCLUSIONS: EtOH treatment increased oxidant stress, TGF-β(1) production, and alternative activation in NR8383 cells. However, GSH supplementation and ablation of TGF-β(1) signaling prevented these effects. This suggested that the EtOH-induced switch to an M2 phenotype was a result of decreased antioxidant availability and increased TGF-β(1) signaling. Preventing EtOH-induced induction of alternative activation may improve alveolar macrophage function in alcoholic subjects and decrease the risk of respiratory infections.
BACKGROUND: Previous studies have shown that chronic ethanol (EtOH) ingestion results in impaired alveolar macrophage function, increased TGF-β(1) production, and decreased antioxidant availability. Similarly, alternative activation (M2 activation) of alveolar macrophages also induces TGF-β(1) production and impairs macrophage function. However, the potential links between EtOH-induced alveolar macrophage derangements, M2 activation, TGF-β(1) production signaling, and oxidant stress have yet to be examined. We hypothesized that EtOH-induced oxidant stress and induction of TGF-β(1) signaling result in alternative activation which subsequently impairs the phagocytic capacity of alveolar macrophages. METHODS: Primary rat alveolar macrophages and the alveolar macrophages cell line NR8383 were treated with 0.08% EtOH ± the antioxidant glutathione (GSH) or a TGF-β(1) neutralizing antibody for 5 days. Outcome measures included TGF-β(1) production, reactive oxygen species (ROS) production, phagocytic capacity, and expression of markers of M2 activation. RESULTS: Chronic EtOH treatment greatly decreased alveolar macrophage phagocytic function, increased ROS production, increased TGF-β(1) , and increased expression of markers of M2 activation. GSH supplementation and inhibition of TGF-β(1) signaling during EtOH treatment prevented these alterations. CONCLUSIONS:EtOH treatment increased oxidant stress, TGF-β(1) production, and alternative activation in NR8383 cells. However, GSH supplementation and ablation of TGF-β(1) signaling prevented these effects. This suggested that the EtOH-induced switch to an M2 phenotype was a result of decreased antioxidant availability and increased TGF-β(1) signaling. Preventing EtOH-induced induction of alternative activation may improve alveolar macrophage function in alcoholic subjects and decrease the risk of respiratory infections.
Authors: Jürgen Rehm; Robin Room; Kathryn Graham; Maristela Monteiro; Gerhard Gmel; Christopher T Sempos Journal: Addiction Date: 2003-09 Impact factor: 6.526
Authors: Rabih I Bechara; Lou Ann S Brown; Jesse Roman; Pratibha C Joshi; David M Guidot Journal: Am J Respir Crit Care Med Date: 2004-04-22 Impact factor: 21.405
Authors: Samantha M Yeligar; Janine M Ward; Frank L Harris; Lou Ann S Brown; David M Guidot; Sushma K Cribbs Journal: AIDS Res Hum Retroviruses Date: 2017-04-24 Impact factor: 2.205
Authors: Samantha M Yeligar; Frank L Harris; C Michael Hart; Lou Ann S Brown Journal: Am J Physiol Lung Cell Mol Physiol Date: 2014-01-17 Impact factor: 5.464
Authors: Eileen Bock O'Halloran; Brenda J Curtis; Majid Afshar; Michael M Chen; Elizabeth J Kovacs; Ellen L Burnham Journal: Alcohol Date: 2015-11-24 Impact factor: 2.405
Authors: Juna V Konomi; Frank L Harris; Xiao-Du Ping; Theresa W Gauthier; Lou Ann S Brown Journal: Alcohol Alcohol Date: 2014-11-03 Impact factor: 2.826
Authors: Jeanette Gaydos; Alicia McNally; Ruixin Guo; R William Vandivier; Philip L Simonian; Ellen L Burnham Journal: Am J Physiol Lung Cell Mol Physiol Date: 2016-01-08 Impact factor: 5.464
Authors: Paul Thevenot; Jordy Saravia; Joseph Giaimo; Kyle I Happel; Tammy R Dugas; Stephania A Cormier Journal: Alcohol Clin Exp Res Date: 2013-06-13 Impact factor: 3.455