Adduction of soluble proteins with malondialdehyde-acetaldehyde (MAA) induces antibody production and enhances T-cell proliferation.
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.
Willis
Monte S
MS
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA. montewillis@juno.com
Klassen
Lynell W
LW
Tuma
Dean J
DJ
Sorrell
Michael F
MF
Thiele
Geoffrey M
GM
D000079:Acetaldehyde / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation / Q000276:immunology / Q000502:physiology*; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects*; D008315:Malondialdehyde / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009113:Muramidase / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D008565:Membrane Proteins; D011506:Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D008315:Malondialdehyde; C421864:hen egg lysozyme; D009113:Muramidase; D000079:Acetaldehyde