Acetaldehyde adducts and autoantibodies against VLDL and LDL in alcoholics.
Acetaldehyde adducts and autoantibodies against VLDL and LDL in alcoholics.
复制标题
DOI：
--
复制
发表时间：
1993-07
影响因子：
6.5
通讯作者：
H. Wehr;M. Rodo;C. Lieber;E. Baraona
中科院分区：
文献类型：
--
作者：
H. Wehr;M. Rodo;C. Lieber;E. Baraona
饮酒可显著增加极低密度脂蛋白（VLDL）的肝脏输出，而降低低密度脂蛋白（LDL）水平和载脂蛋白B。由于apoB-赖氨酸的乙基化使LDL具有免疫原性并加速其清除，并且由于酗酒者产生针对乙酰胆碱-蛋白加合物的抗体，我们寻找针对脂蛋白的抗体。本文用ELISA法测定了10例非酒精性酗酒者和35例近期饮酒者血清中抗VLDL、LDL和高密度脂蛋白（HDL）的IgG、伊加和IgM滴度。酗酒者对VLDL和LDL的IgG滴度高于非酗酒者; VLDL的IgG滴度高于LDL或HDL。使用酗酒者的VLDL和LDL（而不是HDL）得到了最大的反应。伊加和IgM反应性无差异。为了寻找乙醛加合物，我们测量了VLDL、LDL、HDL和残留血清蛋白对兔抗P4502 E1-乙醛加合物IgG的反应性，该IgG识别加合物但不识别未修饰的蛋白质（P4502 E1除外）。含载脂蛋白B的脂蛋白从酗酒者（和在较小程度上非脂蛋白蛋白）与抗加合物IgG的反应比那些非酗酒者更强烈。VLDL的差异显著，LDL的差异较小，HDL的差异不可检测。这表明乙醛在apoB从肝脏分泌之前与apoB反应，并且改变的VLDL在转化为LDL之前被部分去除。总之，酗酒者在含载脂蛋白B的脂蛋白，特别是极低密度脂蛋白中形成乙醛加合物。对这些新抗原的免疫应答可导致VLDL和LDL的加速清除以及VLDL向LDL的转化减少。
Alcohol consumption markedly increases the hepatic output of very low density lipoprotein (VLDL), whereas it decreases the resulting low density lipoprotein (LDL) levels and apolipoprotein B. As ethylation of apoB-lysine renders LDL immunogenic and accelerates their clearance, and as alcoholics develop antibodies against acetaldehyde-protein adducts, we searched for antibodies against lipoproteins. We measured serum IgG, IgA, and IgM titers against VLDL, LDL and high density lipoprotein (HDL) in 10 non-alcoholics and 35 recently drinking alcoholics by ELISA assay. Alcoholics had higher IgG titers than non-alcoholics against VLDL and LDL; these were higher with VLDL than LDL or HDL. Using VLDL and LDL (but not HDL) from alcoholics gave the greatest response. There was no difference in IgA and IgM reactivity. To search for acetaldehyde adducts, we measured the reactivity of VLDL, LDL, HDL, and residual serum proteins against a rabbit anti P4502E1-acetaldehyde adduct IgG, which recognizes the adducts but not the unmodified proteins (except for P4502E1). ApoB-containing lipoproteins from alcoholics (and to a lesser extent non-lipoprotein proteins) reacted with anti-adduct IgG more strongly than those of non-alcoholics. The difference was striking for VLDL, less for LDL, and not detectable for HDL. This suggests that acetaldehyde reacts with apoB prior to its secretion from the liver and that the altered VLDL are partially removed prior to their conversion to LDL. In conclusion, alcoholics develop acetaldehyde adducts in apoB-containing lipoproteins, particularly VLDL. The immune response to these neoantigens could result in accelerated clearance of VLDL and LDL and decreased conversion of VLDL to LDL.