Israel Y, Hurwitz E, Niemelä O, Arnon R
Proc Natl Acad Sci U S A. 1986 Oct;83(20):7923-7. doi: 10.1073/pnas.83.20.7923.
Immunization of mice with acetaldehyde conjugated to human plasma proteins resulted in the production of polyclonal antibodies that reacted with erythrocyte protein-acetaldehyde conjugates, but not with control erythrocyte proteins. Such antibodies recognized erythrocyte protein-acetaldehyde conjugates prepared with 20-100 microM acetaldehyde, concentrations that exist in the blood of alcoholics. The antibodies also recognized acetaldehyde condensation products with synthetic poly-(L-lysine). Immunization with keyhole limpet hemocyanin-acetaldehyde conjugates resulted in antibodies against both plasma protein-acetaldehyde and erythrocyte protein-acetaldehyde conjugates, which did not cross-react with the respective unmodified carrier proteins. Immunization with human erythrocyte protein-acetaldehyde condensates led to the production of antibodies against both the protein moiety as well as the condensate. Monoclonal antibodies with affinities 50 times greater for the condensate than for the carrier protein were produced by hybridization of spleen cells from the immunized mice. Chronic alcohol administration to mice for 45-50 days led to the generation of antibodies that reacted against protein-acetaldehyde conjugates, suggesting that such adducts are formed in vivo and can act as neoantigens. Antibodies against acetaldehyde adducts should be of value in the identification of alcohol consumption and in the study of the biology of the adducts in relation to organ pathology.
用与人血浆蛋白偶联的乙醛免疫小鼠,可产生与红细胞蛋白 - 乙醛偶联物反应,但不与对照红细胞蛋白反应的多克隆抗体。此类抗体可识别用20 - 100微摩尔乙醛制备的红细胞蛋白 - 乙醛偶联物,这是酗酒者血液中存在的浓度。这些抗体还可识别乙醛与合成聚 -(L - 赖氨酸)的缩合产物。用匙孔血蓝蛋白 - 乙醛偶联物免疫可产生针对血浆蛋白 - 乙醛和红细胞蛋白 - 乙醛偶联物的抗体,这些抗体不会与各自未修饰的载体蛋白发生交叉反应。用人红细胞蛋白 - 乙醛缩合物免疫可产生针对蛋白部分以及缩合物的抗体。通过将免疫小鼠的脾细胞杂交,产生了对缩合物的亲和力比对载体蛋白大50倍的单克隆抗体。对小鼠进行45 - 50天的慢性酒精给药,可导致产生与蛋白 - 乙醛偶联物反应的抗体,这表明此类加合物在体内形成并可作为新抗原。针对乙醛加合物的抗体在识别酒精摄入以及研究加合物与器官病理学相关的生物学特性方面应具有价值。