Patel M, Keshavarzian A, Kottapalli V, Badie B, Winship D, Fields J Z
Department of Medicine, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois, USA.
Alcohol Clin Exp Res. 1996 Apr;20(2):275-83. doi: 10.1111/j.1530-0277.1996.tb01640.x.
Neutrophils [polymorphonuclear neutrophils (PMNs)] play a pivotal role in host defense in man. These defenses may be compromised, however, in alcohol users and abusers. We therefore evaluated the effect of ethanol levels (12.5 to 500 mg/dl), on key functions of human PMNs-chemotaxis and production of reactive oxygen species-and on changes in cytosolic-free calcium ([Ca2+]i), a pivotal intracellular mechanism of PMN activation. Ethanol significantly inhibited chemotaxis as evaluated by formyl-methionyl-leucyl-phenylalanine (fMLP)-induced upregulation of surface adhesion molecules (CD11b). fMLP-induced PMN elongation was only inhibited by a very high ethanol concentration of 500 mg/dl. Production of reactive oxygen species by normal PMNs was assessed by either chemiluminescence (CL) for hypochlorous acid or ferricytochrome c reduction (FCR) for superoxide anions. For PMN stimulated by fMLP, ethanol inhibited CL but not FCR. For PMNs activated by phorbol myristate acetate, ethanol inhibited both CL and FCR. Ethanol did not alter baseline [Ca2+]i, as assessed by videomicroscopy using the Ca(2+)-sensing fluorescent dye Fura-2-AM, but did significantly potentiate the increase in peak [Ca2+]i levels that occurs in response to stimulation by fMLP. Calcium channel blockers attenuated ethanol's inhibition of CL. Thus, acute in vitro ethanol, at clinically relevant concentrations, can inhibit several critical aspects of PMN functions. But, in PMNs, unlike neural cells, these inhibitory effects do not seem to be mediated by decreases in Ca2+ influx or in [Ca2+]i.
中性粒细胞[多形核中性粒细胞（PMNs）]在人体宿主防御中起关键作用。然而，酒精使用者和滥用者的这些防御功能可能会受到损害。因此，我们评估了乙醇水平（12.5至500mg/dl）对人中性粒细胞关键功能（趋化性和活性氧生成）以及对细胞溶质游离钙（[Ca2+]i）变化的影响，[Ca2+]i是中性粒细胞激活的关键细胞内机制。通过甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）诱导的表面黏附分子（CD11b）上调评估，乙醇显著抑制趋化性。只有500mg/dl的极高乙醇浓度才会抑制fMLP诱导的中性粒细胞伸长。正常中性粒细胞的活性氧生成通过用于次氯酸的化学发光（CL）或用于超氧阴离子的铁细胞色素c还原（FCR）进行评估。对于由fMLP刺激的中性粒细胞，乙醇抑制CL但不抑制FCR。对于由佛波酯肉豆蔻酸酯乙酸酯激活的中性粒细胞，乙醇同时抑制CL和FCR。通过使用Ca(2+)敏感荧光染料Fura-2-AM的视频显微镜评估，乙醇不会改变基线[Ca2+]i，但确实显著增强了对fMLP刺激的反应中峰值[Ca2+]i水平的增加。钙通道阻滞剂减弱了乙醇对CL的抑制作用。因此，在临床相关浓度下，急性体外乙醇可抑制中性粒细胞功能的几个关键方面。但是，在中性粒细胞中，与神经细胞不同，这些抑制作用似乎不是由Ca2+内流或[Ca2+]i的降低介导的。
