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Alcohol Use Disorders and the Lung pp 63–81Cite as

Alcohol and the Alveolar Macrophage

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Part of the book series: Respiratory Medicine ((RM,volume 14))

Abstract

Compared to nonalcoholics, patients with a history of alcohol-use disorders have increased susceptibility to lung infections, leading to sepsis and in a disproportionately high percentage of cases the development of the acute respiratory distress syndrome. A primary cause for increased risk of respiratory infections in alcoholics is impaired immune function of the alveolar macrophage. Macrophages are key components of innate immunity in various tissues and serve as a first line of defense against invading pathogens by generating pro-inflammatory responses to kill microbes and facilitate the clearance of foreign debris from tissues. Macrophages can be characterized into three phenotypes based on their mechanism of activation and functional characteristics: classical activation (pro-inflammatory), alternative activation, and deactivation (the latter two are anti-inflammatory). Alcohol induces an alternatively activated phenotype in alveolar macrophages, which is characterized by increased oxidative stress, via up-regulation of transforming growth factor beta and NADPH oxidases and phagocytic dysfunction. A range of treatments that increase glutathione and zinc bioavailability, granulocyte–macrophage colony-stimulating factor signaling, or activation of nuclear factor erythroid 2-related factor 2 for the attenuation of alcohol-induced oxidative stress have been identified as strategies that can restore alveolar macrophage immune function in the alcoholic lung.

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Abbreviations

AUD:

Alcohol-use disorder

ARDS:

Acute respiratory distress syndrome

TGFβ:

Transforming growth factor beta

Noxes:

NADPH oxidases

GM-CSF:

Granulocyte/macrophage colony-stimulating factor

Nrf2:

Nuclear factor erythroid 2-related factor 2

ARDI:

Alcohol-Related Disease Impact

SA:

Small aggregate

LA:

Large aggregate

GBS:

Group B Streptococcus pneumoniae

IFNγ:

Interferon gamma

IL:

Interleukin

LPS:

Lipopolysaccharide

SOCS:

Suppressor of cytokine signaling

JAK:

Janus-associated kinase

TLR:

Toll-like receptor

ATF:

Activating transcription factor

TNFα:

Tumor necrosis factor alpha

PPARγ:

Peroxisome proliferator-activated receptor gamma

TZD:

Thiazolidinediones

iNOS:

Inducible nitric oxide synthase

COPD:

Chronic obstructive pulmonary disease

MRC1:

Mannose receptor 1

MHC:

Major histocompatibility complex

MT:

Metallothionine

Arg1:

Arginase 1

ARE:

Antioxidant response element

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Authors and Affiliations

  1. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University, Emory+Children’s Healthcare of Atlanta Center for Developmental Lung Biology, 2015 Uppergate Drive, Atlanta, GA, 30322, USA

    Samantha M. Yeligar M.S., Ph.D., Yan Liang Ph.D. & Lou Ann S. Brown Ph.D.

  2. Department of Medicine, Atlanta Veterans’ Affairs and Emory University Medical Centers, Decatur, GA, USA

    Samantha M. Yeligar M.S., Ph.D.

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  1. Samantha M. Yeligar M.S., Ph.D.
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Correspondence to Lou Ann S. Brown Ph.D. .

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Editors and Affiliations

  1. Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, Georgia, USA

    David M. Guidot

  2. Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Decatur, Georgia, USA

    Ashish J. Mehta

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Yeligar, S.M., Liang, Y., Brown, L.A.S. (2014). Alcohol and the Alveolar Macrophage. In: Guidot, D., Mehta, A. (eds) Alcohol Use Disorders and the Lung. Respiratory Medicine, vol 14. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8833-0_7

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