Production of chemotactic activity for polymorphonuclear leukocytes by cultured rat hepatocytes exposed to ethanol.
Production of chemotactic activity for polymorphonuclear leukocytes by cultured rat hepatocytes exposed to ethanol.
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暴露于乙醇的培养大鼠肝细胞对多形核白细胞产生趋化活性。
DOI：
10.1172/jci111545
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Goldstein,IM
中科院分区：
文献类型：
--
作者：
Perez,HD;Roll,FJ;Bissell,DM;Shak,S;Goldstein,IM
急性酒精性肝炎的特征是多形核白细胞浸润肝实质。作为这种现象的一种可能的解释，我们已经发现，乙醇刺激培养的大鼠肝细胞产生有效的趋化活性。从Sprague-Dawley大鼠肝脏中分离的肝细胞（纯度大于99%）对乙醇（2.0-10 mM）孵育有反应，以时间和浓度依赖性方式将人多形核白细胞的趋化活性释放到培养上清液中。肝细胞与10 mM乙醇孵育6 h后趋化活性最大。在不存在乙醇的情况下检测不到，并且在醇脱氢酶抑制剂4-甲基吡唑或乙醛脱氢酶抑制剂氰胺的存在下减少。乙醇未能刺激大鼠真皮成纤维细胞、肝窦内皮细胞或枯否细胞产生趋化活性。乙醇处理的大鼠肝细胞产生的趋化活性，回收培养上清液中的脂质相后，用氯仿/甲醇提取。氯仿/甲醇提取物的薄层色谱和高效液相色谱表明，趋化因子可能是一种极性脂质。这种趋化性脂质可以部分解释急性酒精性肝炎过程中观察到的肝实质白细胞浸润。
Acute alcoholic hepatitis is characterized by infiltration of the liver parenchyma with polymorphonuclear leukocytes. As a possible explanation for this phenomenon, we have found that ethanol stimulates cultured rat hepatocytes to generate potent chemotactic activity. Hepatocytes (greater than 99% pure), isolated from the livers of Sprague-Dawley rats, responded to incubation with ethanol (2.0-10 mM) by releasing chemotactic activity for human polymorphonuclear leukocytes into culture supernatants in a time- and concentration-dependent fashion. Chemotactic activity was maximal after incubation of hepatocytes with 10 mM ethanol for 6 h. It was undetectable in the absence of ethanol and was reduced in the presence of either the alcohol dehydrogenase inhibitor, 4-methylpyrazole, or the acetaldehyde dehydrogenase inhibitor, cyanamide. Ethanol failed to stimulate generation of chemotactic activity by either rat dermal fibroblasts, hepatic sinusoidal endothelial cells, or Kupffer cells. The chemotactic activity generated by ethanol-treated rat hepatocytes was recovered from culture supernatants in the lipid phase after extraction with chloroform/methanol. Thin-layer chromatography and high performance liquid chromatography of chloroform/methanol extracts demonstrated that the chemotactic factor probably is a polar lipid. This chemotactic lipid may account, in part, for the leukocytic infiltration of the liver parenchyma that is observed during the course of acute alcoholic hepatitis.