Shiratori Y, Takada H, Hai K, Kiriyama H, Mawet E, Komatsu Y, Niwa Y, Matsumura M, Shiina S, Kawase T
Department of Gastroenterology and Hepatology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan.
Dig Dis Sci. 1994 Jul;39(7):1569-75. doi: 10.1007/BF02088066.
In an attempt to clarify a mechanism of neutrophil infiltration in the liver of alcoholics and possible therapeutic effect of antiallergic agents on accumulation of these cells in the liver, we investigated chemotaxis of neutrophils by stimulation of a chemotactic factor released from rat hepatocytes exposed to ethanol. When hepatocytes were incubated with more than 30 mM ethanol for 24 hr, chemotactic activity for both rat and human neutrophils was demonstrated in the conditioned medium. An enhanced chemotactic activity of the conditioned medium was reduced in the presence of antibody against KC/gro protein, one of the interleukin-8-related cytokines in rodents. Antiallergic agents such as azelastine or ketotifen at a concentration of > 0.01 microM markedly reduced chemotaxis of neutrophils. Prednisolone at a concentration of > 10 microM also reduced chemotaxis of neutrophils. These results suggest that neutrophil accumulation in the liver of human alcoholics could be induced by a chemotactic factor produced by the ethanol-treated hepatocytes and that antiallergic agents could be effective against the extent of alcoholic hepatitis by reducing chemotaxis of neutrophils.
为了阐明酒精性肝病患者肝脏中中性粒细胞浸润的机制以及抗过敏药物对这些细胞在肝脏中积聚的可能治疗作用，我们通过刺激暴露于乙醇的大鼠肝细胞释放的趋化因子来研究中性粒细胞的趋化性。当肝细胞与超过30 mM乙醇孵育24小时时，条件培养基中显示出对大鼠和人类中性粒细胞的趋化活性。在存在针对KC/gro蛋白（啮齿动物中白细胞介素-8相关细胞因子之一）的抗体时，条件培养基增强的趋化活性降低。浓度> 0.01 microM的抗过敏药物如氮卓斯汀或酮替芬显著降低中性粒细胞的趋化性。浓度> 10 microM的泼尼松龙也降低中性粒细胞的趋化性。这些结果表明，乙醇处理的肝细胞产生的趋化因子可诱导人类酒精性肝病患者肝脏中的中性粒细胞积聚，并且抗过敏药物可通过降低中性粒细胞的趋化性有效对抗酒精性肝炎的程度。
