Walia A S, Pruitt K M, Rodgers J D, Lamon E W
Immunopharmacology. 1987 Feb;13(1):11-24. doi: 10.1016/0162-3109(87)90023-3.
The effects of ethanol on murine spleen cell-mediated lysis have been studied. Concentrations of 5.5-176 mM ethanol produced progressive inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). Binding of spleen cells to antibody-sensitized target cells was not inhibited by comparable concentrations of ethanol. Kinetic analysis revealed decreased rates of lysis with increasing concentrations of ethanol. Changes of effector to target cell ratios revealed an inhibition of maximum lysis and decreased lytic efficiency in the presence of 88 mM ethanol. Preincubation experiments showed the inhibitory effect of ethanol to be reversible. Macrophage-depleted spleen cells appeared to be as susceptible to inhibition by ethanol as unfractionated spleen cells. Ethanol also inhibited natural killer and alloimmune cytotoxic T cell activity. The ADCC data were analysed by using a mathematical model which incorporates the kinetics of lysis, dose-response relationships, heterogeneity of the lytic effectors, reversibility of inhibition and ethanol loss during incubation. An inhibition constant (KI) of 373 mM-2 when two ethanol molecules interact with the site of inhibition was calculated. 50% inhibition of lysis is produced by 52 mM (0.24%) ethanol. The results are consistent with a model which assumes that lysis is due to a critical number of interactions which ultimately trigger the lytic event. Alcohol interferes with lysis by reacting with sites which are required for triggering the lytic event. Although the molecular details of the mechanism of inhibition are as yet undefined, we infer that ethanol inhibits ADCC at the programming for lysis or the lethal hit stages.
已对乙醇对小鼠脾细胞介导的细胞裂解作用进行了研究。浓度为5.5 - 176 mM的乙醇可逐渐抑制抗体依赖性细胞介导的细胞毒性（ADCC）。相当浓度的乙醇不会抑制脾细胞与抗体致敏靶细胞的结合。动力学分析表明，随着乙醇浓度的增加，裂解速率降低。效应细胞与靶细胞比例的变化显示，在88 mM乙醇存在下，最大裂解受到抑制，裂解效率降低。预孵育实验表明乙醇的抑制作用是可逆的。巨噬细胞耗竭的脾细胞似乎与未分离的脾细胞一样易受乙醇抑制。乙醇还抑制自然杀伤细胞和同种异体免疫细胞毒性T细胞活性。通过使用一个数学模型对ADCC数据进行分析，该模型纳入了裂解动力学、剂量反应关系、裂解效应器的异质性、抑制的可逆性以及孵育过程中乙醇的损失。当两个乙醇分子与抑制位点相互作用时，计算出抑制常数（KI）为373 mM⁻²。52 mM（0.24%）的乙醇可产生50%的裂解抑制。结果与一个模型一致，该模型假设裂解是由于最终触发裂解事件的关键数量的相互作用所致。酒精通过与触发裂解事件所需的位点反应来干扰裂解。尽管抑制机制的分子细节尚未明确，但我们推断乙醇在裂解编程或致死打击阶段抑制ADCC。
