Gorski N P, Nouraldin H, Dube D M, Preffer F I, Dombkowski D M, Villa E M, Lewandrowski K B, Weiss R D, Hufford C, Laposata M
Department of Pathology, Massachusetts General Hospital, Boston 02114, USA.
Alcohol Clin Exp Res. 1996 Apr;20(2):268-74. doi: 10.1111/j.1530-0277.1996.tb01639.x.
Fatty acid ethyl esters (FAEEs), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol-induced organ damage. It has been shown that FAEE synthase, the enzyme responsible for the formation of FAEE, is present selectively in the organs commonly damaged by ethanol abuse. Recently, we have made the observation that FAEEs are also present in the serum after ethanol ingestion. The current study was performed to determine whether cellular elements of the blood and/or plasma are capable of synthesizing FAEEs from fatty acids and ethanol.
Heparinized blood samples were collected from 10 healthy volunteers, and the red blood cells, platelets, plasma, and several white blood cell populations were assayed for FAEE synthase activity. Blood samples from control subjects and individuals admitted to an alcoholic detoxification unit at a local hospital were also assayed for FAEE synthase activity.
We observed that the FAEE synthase activity is present in whole blood, primarily within white blood cells. Fractionation of the white blood cells revealed that the lymphocyte-monocyte fraction isolated using Ficoll-hypaque contained approximately 3.5-fold higher activity than the granulocyte fraction. The cell type that contained the highest FAEE synthase activity (1220 pmol/hr/10(6) cells) was the natural killer (NK) cell population. B cells contained approximately 40% of the enzyme activity found in NK cells, and the B-cell activity was slightly greater than that found in CD4+ and CD8+ T cells. Having shown that FAEE synthase exists in a blood cell, we subsequently demonstrated that alcoholic individuals have approximately half the white blood cell FAEE synthase activity of that found in normal controls. We also demonstrated that white blood cell FAEE synthase could be induced nearly 2-fold upon ingestion of 2 oz of scotch whiskey for 6 days. The enzyme activity returned to baseline levels despite ingestion of 2 oz of scotch whiskey/day for 3 additional days.
These data indicate that ethanol ingestion results in increased FAEE production, particularly by NK cells. FAEE synthesis after ethanol ingestion may explain the presence of FAEE in the serum. The lower enzyme activity observed in white blood cells of alcoholics from a detoxification center may be the result of years of ethanol abuse or it may be that alcoholics congenitally have low levels of FAEE synthase. If the latter is true, this finding may explain in part the genetic predisposition of many alcoholic individuals to ethanol abuse.
脂肪酸乙酯（FAEEs）是乙醇与脂肪酸的酯化产物，被认为是乙醇诱导器官损伤的介质。研究表明，负责FAEE形成的酶——FAEE合酶，选择性地存在于因乙醇滥用而常见受损的器官中。最近，我们观察到乙醇摄入后血清中也存在FAEEs。进行本研究以确定血液和/或血浆中的细胞成分是否能够从脂肪酸和乙醇合成FAEEs。
从10名健康志愿者采集肝素化血液样本，对红细胞、血小板、血浆和几个白细胞群体进行FAEE合酶活性检测。还对对照组受试者以及当地一家医院酒精解毒科收治个体的血液样本进行FAEE合酶活性检测。
我们观察到FAEE合酶活性存在于全血中，主要存在于白细胞内。白细胞分级分离显示，使用聚蔗糖-泛影葡胺分离的淋巴细胞-单核细胞组分的活性比粒细胞组分高约3.5倍。FAEE合酶活性最高的细胞类型（1220 pmol/小时/10⁶个细胞）是自然杀伤（NK）细胞群体。B细胞的酶活性约为NK细胞的40%，且B细胞的活性略高于CD4⁺和CD8⁺T细胞。在证明FAEE合酶存在于血细胞中之后，我们随后证明酗酒个体白细胞中的FAEE合酶活性约为正常对照组的一半。我们还证明，连续6天摄入2盎司苏格兰威士忌后，白细胞FAEE合酶可被诱导增加近2倍。尽管之后又连续3天每天摄入2盎司苏格兰威士忌，但酶活性恢复到基线水平。
这些数据表明，乙醇摄入会导致FAEE生成增加，尤其是NK细胞。乙醇摄入后FAEE的合成可能解释了血清中FAEE的存在。在解毒中心的酗酒者白细胞中观察到的较低酶活性可能是多年乙醇滥用的结果，也可能是酗酒者先天性FAEE合酶水平较低。如果后者属实，这一发现可能部分解释了许多酗酒个体对乙醇滥用的遗传易感性。
