Rubin E M, Martin A A, Thung S N, Gerber M A
Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Pathol. 1995 Aug;147(2):397-404.
Regeneration in human liver is characterized in part by the formation of ductular structures, so-called ductular hepatocytes in massive hepatic necrosis and bile ductules in mechanical biliary obstruction. In an attempt to characterize the liver regenerative process, we performed image analysis and immunohistochemical staining of the ductular structures in these well defined human liver disorders, 13 cases of massive hepatic necrosis and 9 cases of mechanical biliary obstruction. The proliferation index was determined and the expression of several antigens was localized by immunohistochemical staining using antibodies to alpha-fetoprotein, alpha-1-antitrypsin, albumin, and cytokeratin 19. The ductular structures in adult human liver were compared with the developing ductal plates in 11 fetal livers, ranging in age from 9 to 36 weeks of gestation. Image analysis demonstrated that the mean total area, mean nuclear area, and mean cell size of ductular hepatocytes were significantly larger than those of bile ductules (p < 0.05). The proliferation index of ductular hepatocytes and bile ductules was significantly higher than that of hepatocytes of normal livers (p < 0.02). Bile ducts, bile ductules in mechanical biliary obstruction, ductular hepatocytes in massive hepatic necrosis, and the ductal plate cells in fetal liver showed strong staining for cytokeratin 19, which characterizes intermediate filaments associated with bile duct epithelial cells. Albumin, a liver-specific protein, and alpha-1-antitrypsin, a protease inhibitor, were strongly expressed in ductal plate cells of fetal liver, hepatocytes, and ductular hepatocytes, whereas bile duct cells and bile ductules were negative for albumin. In summary, ductular hepatocytes demonstrate morphometric and immunophenotypic features of both hepatocytes and biliary epithelial cells, whereas bile ductules share characteristics primarily with fetal ductal plates and mature bile ducts. These findings suggest that ductular hepatocytes in massive hepatic necrosis may serve as bipotential progenitor cells, and bile ductules in mechanical biliary obstruction are related to ductal plates of fetal liver.
人类肝脏再生的部分特征是形成导管样结构，即在大片肝坏死中所谓的导管样肝细胞以及在机械性胆管梗阻中出现的胆小管。为了描述肝脏再生过程，我们对这些明确的人类肝脏疾病中的导管样结构进行了图像分析和免疫组化染色，包括13例大片肝坏死和9例机械性胆管梗阻。通过使用针对甲胎蛋白、α1抗胰蛋白酶、白蛋白和细胞角蛋白19的抗体进行免疫组化染色来确定增殖指数并定位几种抗原的表达。将成人肝脏中的导管样结构与11例胎龄为9至36周的胎儿肝脏中发育中的导管板进行比较。图像分析表明，导管样肝细胞的平均总面积、平均核面积和平均细胞大小显著大于胆小管（p<0.05）。导管样肝细胞和胆小管的增殖指数显著高于正常肝脏的肝细胞（p<0.02）。胆管、机械性胆管梗阻中的胆小管、大片肝坏死中的导管样肝细胞以及胎儿肝脏中的导管板细胞对细胞角蛋白19呈强染色，细胞角蛋白19是与胆管上皮细胞相关的中间丝的特征性蛋白。白蛋白是一种肝脏特异性蛋白，α1抗胰蛋白酶是一种蛋白酶抑制剂，在胎儿肝脏的导管板细胞、肝细胞和导管样肝细胞中强烈表达，而胆管细胞和胆小管对白蛋白呈阴性。总之，导管样肝细胞表现出肝细胞和胆管上皮细胞的形态学和免疫表型特征，而胆小管主要与胎儿导管板和成熟胆管具有共同特征。这些发现表明，大片肝坏死中的导管样肝细胞可能作为双能祖细胞，机械性胆管梗阻中的胆小管与胎儿肝脏的导管板有关。
