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Cited by 44Atherosclerosis and Cardiovascular DiseasesT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

T cell proliferative responses to malondialdehyde–acetaldehyde haptenated protein are scavenger receptor mediated

Willis, Monte S, Thiele, Geoffrey M, Tuma, Dean J, Klassen, Lynell W·2003·International Immunopharmacology
DOI 10.1016/s1567-5769(03)00136-x
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Abstract

Malondialdehyde-acetaldehyde (MAA) haptenated proteins have been described in disease processes related to prolonged oxidative stress (via malondialdehyde production), such as alcohol liver disease (ALD), non-alcoholic non-steatohepatitis (NASH) and atherosclerosis. Experimentally, high titer IgG1 antibody responses are seen after immunization without adjuvant; however, T cell proliferative responses and the role of scavenger receptors in this immunogenicity has not previously been described. In this study, T cell proliferative responses to the carrier protein, but not the MAA hapten itself, were identified in vitro. Moreover, these T proliferative responses were inhibited when MAA-hen egg lysozyme (HEL) was co-immunized with excess scavenger receptor ligand polyG (poly-guanylic acid), implicating the role of (a) scavenger receptor(s) in initiating the T helper cell response. Activated B cells were unable to process and present MAA-HEL preferentially to T cells, while thioglycollate-elicited (but not Con A-elicited) macrophages and dendritic cells (DC) did so with approximately 32-fold less MAA-HEL than native antigen necessary to initiate equal proliferative responses. While this preferential processing and presentation may be related to several factors, preferential binding of MAA haptenated proteins mediated by scavenger receptors may be one mechanism. IL-4 was absent from the supernatants of T proliferative assays despite a strong IgG1 response in vivo, although the TH2 cytokines IL-6 and IL-10 were expressed. Since the modification of proteins by the MAA have previously been shown to occur after ethanol consumption in vivo, the ability of MAA haptens to experimentally enhance immune responses, specifically humoral and T cell responses, may represent mechanisms by which autoimmune phenomena found in ALD occur.

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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 [225]

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Authors
Willis, M. S., Thiele, G. M., Tuma, D. J., & Klassen, L. W.
Affiliations
  • Omaha VA Medical Center (US)
  • Nebraska Medical Center (US)
Corresponding author
Willis, Monte S
ORCID
Venue
International Immunopharmacology
Publisher
Elsevier BV
Published
2003-10
Volume
3
Issue
10-11
Pages
1381-1399
ISSN
1567-5769 (ISSN-L)
DOI
10.1016/s1567-5769(03)00136-x
OpenAlex
W1963720482
Cited by
44
References
66
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 1
FWCI
0.98
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • International Immunopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • 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 › Atherosclerosis and Cardiovascular Diseases
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
haptens, T cell proliferation, scavenger receptors, hen egg white lysozyme, antigen processing and presentation, macrophages, dendritic cells, alcoholic liver disease, oxidative stress, autoimmunity, interleukin-6, IL-10, IL-4, IgG1 antibodies
MeSH terms
Acetaldehyde, Animals, Cell Division, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Female, Haptens, Lymph Nodes, Malondialdehyde, Membrane Proteins, Mice, Inbred BALB C, Muramidase, Receptors, Immunologic, Spleen, T-Lymphocytes, Cytokines, Macrophages, Peritoneal, Receptors, Lipoprotein, Receptors, Scavenger, Scavenger Receptors, Class B, Mice

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