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Cited by 56Immunotoxicology and immune responsesAlcohol Consumption and Health EffectsT-cell and B-cell Immunology

Adduction of Soluble Proteins with Malondialdehyde‐Acetaldehyde (MAA) Induces Antibody Production and Enhances T‐Cell Proliferation

Willis, Monte S., Klassen, Lynell W., Tuma, Dean J., Sorrell, Michael F., Thiele, Geoffrey M.·2002·Alcoholism: Clinical and Experimental Research
DOI 10.1111/j.1530-0277.2002.tb02436.x
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Abstract

Background: The alcohol metabolites malondialdehyde and acetaldehyde can combine to form stable adducts (MAA) which are found in the livers of humans and rats after significant alcohol ingestion. While adducted proteins induce antibody responses in the absence of adjuvants, the mechanisms by which these responses occur are unknown. Thus, it was the purpose of these studies to investigate how MAA modification stimulates antibody and T‐cell responses in the absence of adjuvants. Methods: Hen egg lysozyme (HEL) was modified with increasing levels of MAA and was used as an immunogen, and antibody and T‐cell responses were determined. The role of scavenger receptors in the immunogenicity of MAA‐adducted proteins was also investigated. Results: Maximum antibody response was induced after immunization with 1.8 nM MAA/nM HEL, and was primarily an IgG1 response to HEL as determined by inhibition ELISAs. T‐cell proliferative responses after immunization with HEL‐MAA were solely to HEL. Immunization with a scavenger receptor ligand in conjunction with HEL‐MAA increased the predominant IgG1 response and sharply decreased the IgG2a response by approximately 50%. Binding of HEL‐MAA by splenocytes was determined by flow cytometry to be approximately 15% greater than HEL alone, showing a doubling of the geometric mean fluorescence. Also, most of the cells that bound HEL‐MAA were class II positive, indicating that antigen‐presenting cells can bind the MAA‐adducted HEL, and potentially initiate immune responses. Conclusions: MAA modification of proteins induces antibody and T‐cell proliferative responses in vivo. Initial studies suggest that these responses may be mediated by scavenger receptors that recognize MAA‐adducted proteins. This suggests a mechanism by which proteins modified with oxidative products associated with chronic ethanol consumption may alter immune responses that may play an active role in the development and/or progression of alcoholic liver disease.

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Crossref · 10.1111/j.1530-0277.2002.tb02436.x

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  • MAA adducts are found in HSCs, liver sinusoidal endothelial cells, and Kupffer cells in ALD models; they stimulate transformation of HSCs into activated myofibroblasts, resulting in elevated production of profibrotic factors such as PDGF, and can induce proinflammatory cytokines such as TNF-α, IL-12, IL-18, and MIF.

    “In addition to individual AA and MDA adducts, MAA adducts (AA-MDA-protein hybrid adducts) are found in HSCs, liver sinusoidal endothelial cells, and Kupffer cells in ALD models.”

    From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [223]

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Authors
Willis, M. S., Klassen, L. W., Tuma, D. J., Sorrell, M. F., & Thiele, G. M.
Affiliations
Omaha VA Medical Center (US)
Corresponding author
Willis, Monte S.
ORCID
Venue
Alcoholism: Clinical and Experimental Research
Publisher
Wiley
Published
2002-01
Volume
26
Issue
1
Pages
94-106
ISSN
  • 0145-6008 (ISSN-L)
  • 1530-0277
DOI
10.1111/j.1530-0277.2002.tb02436.x
OpenAlex
W2069559661
Cited by
56
References
56
Citations by year
2023: 1 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 1
FWCI
1.32
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1561 d)
Locations
  • Alcoholism Clinical and Experimental Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Università di Bologna
  • National Institutes of Health (5r01aa007818-06, 1f30aa005487-01)
  • National Institute on Alcohol Abuse and Alcoholism (R29-AA10435, F30AA05487, R01AA07818, R29AA010435)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
protein adduction, alcohol metabolites, hen egg white lysozyme, antibody response, T cell proliferation, scavenger receptors, IgG1, IgG2a, antigen-presenting cells, chronic alcohol consumption, alcoholic liver disease, oxidative stress, adjuvant-free immunization
MeSH terms
Acetaldehyde, Adjuvants, Immunologic, Animals, Antibody Formation, Female, Lymphocyte Activation, Malondialdehyde, Membrane Proteins, Mice, Inbred BALB C, Mice, Inbred C3H, Muramidase, Proteins, Receptors, Immunologic, Solubility, T-Lymphocytes, Receptors, Lipoprotein, Receptors, Scavenger, Scavenger Receptors, Class B, Mice

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