Breitmeier Dirk, Becker Nina, Weilbach Christian, Albrecht Knut, Scheinichen Dirk, Panning Bernhard, Schneider Udo, Jüttner Björn
Institute of Legal Medicine, Medical School Hannover, Hannover, Germany.
Alcohol Clin Exp Res. 2008 Oct;32(10):1708-13. doi: 10.1111/j.1530-0277.2008.00748.x. Epub 2008 Jul 9.
Polymorphonuclear, neutrophil granulocytes (PMN) play a major role in the control of infections, and people who abuse alcohol are susceptible to infections. Resistance against infections ensues intracellularly following initial phagocytosis of microorganisms with the oxygen-dependent respiratory burst, the key enzyme of which is the respiratory burst oxidase, whereby oxygen radicals are produced for microbial destruction. To date there is insufficient information available in connection with the process of impaired defence against infection in patients suffering from alcohol dependence. Therefore, our investigation was carried out to determine the influence of alcohol exposition on the formation of oxygen radicals and the respiratory burst.
4.5 ml of whole blood was taken from 10 healthy adults and 10 patients suffering from alcohol dependence. An additional 3.5 ml of whole blood was taken from the alcoholic patients for determination of the blood alcohol concentration. The respiratory burst of PMN was tested using the Four-Colour-Continuous Flow Cytometer. Each experimental procedure consisted of 4 test samples [negative controls, Escherichia coli, FMLP-supplement (N-formyl-l-methionyl-l-leucyl-l-phenylalanin), PMA-supplement (phorbol-12-myristate-13-acetate)]. Differing concentrations of ethanol were also introduced to each of the tests performed (0.20 to 4.00 g/l).
Ethanol revealed a marked decrease of burst activity in those patients suffering from alcoholism with increased alcohol concentration. A dependence between the burst activity and the ethanol concentration was seen to be statistically significant. This effect was only evident after stimulation with E. coli and FMLP in those patients with alcohol dependence.
The results presented in this study show an impairment in the function of PMN in those patients addicted to alcohol due to the decrease in burst activity. In view of the results of the different stimuli, the second-messenger effects were not evident. A clarification of this phenomenon could well be assumed as an allosteric receptor effect on the burst oxidase, namely, a direct effect on the phagocytosis interaction between circulating granulocytes and causative organisms.
多形核中性粒细胞（PMN）在控制感染中起主要作用，而酗酒者易受感染。在微生物被初始吞噬后，通过氧依赖性呼吸爆发在细胞内产生抗感染能力，其关键酶是呼吸爆发氧化酶，由此产生氧自由基以破坏微生物。迄今为止，关于酒精依赖患者抗感染防御受损过程的信息不足。因此，我们进行了这项研究以确定酒精暴露对氧自由基形成和呼吸爆发的影响。
从10名健康成年人和10名酒精依赖患者中采集4.5毫升全血。另外从酒精依赖患者中采集3.5毫升全血用于测定血液酒精浓度。使用四色连续流式细胞仪检测PMN的呼吸爆发。每个实验程序包括4个测试样本[阴性对照、大肠杆菌、FMLP补充剂（N-甲酰基-L-甲硫氨酰-L-亮氨酰-L-苯丙氨酸）、PMA补充剂（佛波醇-12-肉豆蔻酸酯-13-乙酸酯）]。在每个进行的测试中还引入了不同浓度的乙醇（0.20至4.00克/升）。
乙醇显示，酒精浓度升高的酗酒患者的爆发活性显著降低。爆发活性与乙醇浓度之间的相关性在统计学上具有显著意义。这种效应仅在酒精依赖患者中经大肠杆菌和FMLP刺激后才明显。
本研究结果表明，由于爆发活性降低，酗酒患者的PMN功能受损。鉴于不同刺激的结果，第二信使效应不明显。可以很好地推测，这种现象的一个解释是对爆发氧化酶的变构受体效应，即对循环粒细胞与致病生物体之间吞噬作用的直接影响。
