Ozaki Masayuki, Ogata Masanori, Nandate Koichiroh, Kawasaki Takashi, Sata Takeyoshi
Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
J Trauma. 2007 Oct;63(4):770-4. doi: 10.1097/01.ta.0000235887.91107.61.
Acute alcohol intoxication is associated with increased susceptibility to infection. In host defense, the expression of adhesion molecules such as beta2-integrin and l-selectin on leukocytes is involved in leukocyte migration to inflamed organ tissue. To elucidate the mechanisms underlying the immunosuppressive effects of ethanol, we investigated whether ethanol pretreatment may influence the changes in adhesion molecule expression induced by lipopolysaccharide (LPS) or interleukin (IL)-8 in human whole blood.
Ethanol was added to samples of human whole blood (final concentration: 0%, 0.2%, 0.4%, and 0.8%). Samples were assigned to an unstimulated group and an LPS-stimulated group. In another set of experiments, stimulation was induced by IL-8. After fluorescence labeling of alphaM-subunit of beta2-integrin (CD11b) and l-selectin (CD62L), the expression of CD11b and CD62L were measured using flow cytometry.
Stimulation with LPS significantly upregulated CD11b expression (5.9 +/- 0.9 to 16.3 +/- 1.8, p < 0.05). Ethanol inhibited this LPS-induced upregulation of CD11b (p < 0.001). Stimulation with IL-8 significantly upregulated CD11b expression (5.3 +/- 1.7 to 7.5 +/- 2.7, p < 0.01) and this IL-8-induced upregulation of CD11b was also inhibited by ethanol pretreatment (p < 0.001). In contrast, ethanol did not modify CD62L expression in either unstimulated or stimulated groups.
The impairment of CD11b expression on leukocytes suggests that alcohol intake interferes with the migration of leukocytes to sites of inflammation, which may explain, in part, why alcohol intoxication increases susceptibility to infection.
急性酒精中毒与感染易感性增加有关。在宿主防御中，白细胞上的黏附分子如β2整合素和L-选择素的表达参与白细胞向炎症器官组织的迁移。为了阐明乙醇免疫抑制作用的潜在机制，我们研究了乙醇预处理是否会影响脂多糖（LPS）或白细胞介素（IL）-8诱导的人全血中黏附分子表达的变化。
将乙醇添加到人全血样本中（终浓度：0%、0.2%、0.4%和0.8%）。样本分为未刺激组和LPS刺激组。在另一组实验中，用IL-8诱导刺激。对β2整合素（CD11b）的αM亚基和L-选择素（CD62L）进行荧光标记后，使用流式细胞术测量CD11b和CD62L的表达。
LPS刺激显著上调CD11b表达（从5.9±0.9至16.3±1.8，p<0.05）。乙醇抑制了LPS诱导的CD11b上调（p<0.001）。IL-8刺激显著上调CD11b表达（从5.3±1.7至7.5±2.7，p<0.01），乙醇预处理也抑制了IL-8诱导的CD11b上调（p<0.001）。相反，乙醇在未刺激组或刺激组中均未改变CD62L表达。
白细胞上CD11b表达的受损表明饮酒会干扰白细胞向炎症部位的迁移，这可能部分解释了为什么酒精中毒会增加感染易感性。
