Malondialdehyde–Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti-MAA Antibodies

Muna Sapkota, Ellen L. Burnham, Jane M. Devasure, Jenea M. Sweeter, Carlos D. Hunter, Michael J. Duryee, Lynell Warren Klassen, Kusum Kharbanda, Joseph Harold Sisson, Geoffrey Milton Thiele, Todd A Wyatt

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUDs) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde–acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Methods: Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (−AUD/+smoke), AUD without smoke (+AUD/−smoke), and non-AUD/nonsmokers (−AUD/−smoke). Results: We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke versus −AUD/−smoke. No significant increase in MAA adducts was observed in −AUD/+smoke or in +AUD/−smoke compared to −AUD/−smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After 1 week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. Conclusions: MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking.

Original languageEnglish (US)
Pages (from-to)2093-2099
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume41
Issue number12
DOIs
StatePublished - Dec 2017

Fingerprint

Anti-Idiotypic Antibodies
Smoke
Alcohols
Lung
Proteins
Tobacco Products
Acetaldehyde
Malondialdehyde
Alcoholism
Antibodies
Tobacco
Serum
Immunoglobulin A
Metabolites
Lung Diseases
Antibody Formation
Metabolism
Epitopes
Pneumonia
Ethanol

Keywords

  • Adduct
  • Alcohol
  • Cigarette Smoke
  • IgA
  • Macrophage

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

@article{fec050d12e454a4cac90e77157ce9bcd,
title = "Malondialdehyde–Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti-MAA Antibodies",
abstract = "Background: Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUDs) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde–acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Methods: Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (−AUD/+smoke), AUD without smoke (+AUD/−smoke), and non-AUD/nonsmokers (−AUD/−smoke). Results: We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke versus −AUD/−smoke. No significant increase in MAA adducts was observed in −AUD/+smoke or in +AUD/−smoke compared to −AUD/−smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After 1 week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. Conclusions: MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking.",
keywords = "Adduct, Alcohol, Cigarette Smoke, IgA, Macrophage",
author = "Muna Sapkota and Burnham, {Ellen L.} and Devasure, {Jane M.} and Sweeter, {Jenea M.} and Hunter, {Carlos D.} and Duryee, {Michael J.} and Klassen, {Lynell Warren} and Kusum Kharbanda and Sisson, {Joseph Harold} and Thiele, {Geoffrey Milton} and Wyatt, {Todd A}",
year = "2017",
month = "12",
doi = "10.1111/acer.13509",
language = "English (US)",
volume = "41",
pages = "2093--2099",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "12",

}

TY - JOUR

T1 - Malondialdehyde–Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti-MAA Antibodies

AU - Sapkota, Muna

AU - Burnham, Ellen L.

AU - Devasure, Jane M.

AU - Sweeter, Jenea M.

AU - Hunter, Carlos D.

AU - Duryee, Michael J.

AU - Klassen, Lynell Warren

AU - Kharbanda, Kusum

AU - Sisson, Joseph Harold

AU - Thiele, Geoffrey Milton

AU - Wyatt, Todd A

PY - 2017/12

Y1 - 2017/12

N2 - Background: Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUDs) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde–acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Methods: Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (−AUD/+smoke), AUD without smoke (+AUD/−smoke), and non-AUD/nonsmokers (−AUD/−smoke). Results: We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke versus −AUD/−smoke. No significant increase in MAA adducts was observed in −AUD/+smoke or in +AUD/−smoke compared to −AUD/−smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After 1 week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. Conclusions: MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking.

AB - Background: Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUDs) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde–acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Methods: Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (−AUD/+smoke), AUD without smoke (+AUD/−smoke), and non-AUD/nonsmokers (−AUD/−smoke). Results: We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke versus −AUD/−smoke. No significant increase in MAA adducts was observed in −AUD/+smoke or in +AUD/−smoke compared to −AUD/−smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After 1 week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. Conclusions: MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking.

KW - Adduct

KW - Alcohol

KW - Cigarette Smoke

KW - IgA

KW - Macrophage

UR - http://www.scopus.com/inward/record.url?scp=85032983459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032983459&partnerID=8YFLogxK

U2 - 10.1111/acer.13509

DO - 10.1111/acer.13509

M3 - Article

C2 - 28941289

AN - SCOPUS:85032983459

VL - 41

SP - 2093

EP - 2099

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 12

ER -