Detection of circulating antibodies to malondialdehyde-acetaldehyde adducts in ethanol-fed rats.
OBJECTIVE
Malondialdehyde and acetaldehyde react together with proteins and form hybrid protein conjugates designated as MAA adducts, which have been detected in livers of ethanol-fed rats. The aim of this study was to examine the immune response to MAA adducts and other aldehyde adducts during long-term ethanol exposure.


METHODS
Rats were pair-fed for 7 months with a liquid diet containing either ethanol or isocaloric carbohydrate. Circulating antibody titers against MAA adducts and acetaldehyde adducts were measured and characterized in these animals.


RESULTS
A significant increase in antibody titers against MAA-adducted proteins was observed in the ethanol-fed animals. Competitive inhibitions of antibody binding indicated that the circulating antibodies against MAA-modified proteins in the ethanol-fed rats recognized mainly a specific, chemically defined MAA epitope. Antibody titers to reduced and nonreduced acetaldehyde adducts were very low, and no significant differences were observed between ethanol-fed and control animals. Significant plasma immunoreactivity to not only MAA-adducted but also unmodified rat liver proteins (cytosol, microsomes, and especially plasma membrane) were also observed in the ethanol-fed rats.


CONCLUSIONS
Long-term ethanol feeding generates circulating antibodies not only against MAA epitopes but possibly also against unmodified, native (self) protein epitopes, suggesting that MAA adducts could trigger harmful autoimmune responses.
Department of Veterans Affairs Alcohol Research Center and Departments of Internal Medicine and Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
D
D
Xu
G M
GM
Thiele
J L
JL
Beckenhauer
L W
LW
Klassen
M F
MF
Sorrell
D J
DJ
Tuma
D000079:Acetaldehyde / Q000276:immunology*; D000437:Alcoholism / Q000097:blood / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood*; D000917:Antibody Formation; D000918:Antibody Specificity; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D008315:Malondialdehyde / Q000276:immunology*; D011506:Proteins / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D000906:Antibodies; D011506:Proteins; D008315:Malondialdehyde; D000079:Acetaldehyde