Sakaguchi H, Seki S, Tsubouchi H, Daikuhara Y, Niitani Y, Kobayashi K
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Hepatology. 1994 May;19(5):1157-63.
Human hepatocyte growth factor has been purified from the plasma of patients with fulminant liver failure, but where this factor is produced in organs or cells of subjects with liver diseases is unknown. Therefore, we used a monoclonal antibody to human hepatocyte growth factor to stain cells in three normal and 29 diseased liver tissues by immunohistochemical techniques. By light microscopy, the immunostained cells seemed to be polymorphonuclear leukocytes because of their segmented nuclei. Some biliary epithelial cells also were stained. Electron microscopy confirmed that the immunostained cells with segmented nuclei were polymorphonuclear leukocytes and that the stained grains were on the membranes of rough endoplasmic reticulum, around specific or azurophilic granules and in the cell sap. Stained grains in the biliary epithelial cells were found sporadically on the inside and outside of the membranes of rough endoplasmic reticulum near the nuclei. Human hepatocyte growth factor is now known to be the same protein as scatter factor and tumor cytotoxic factor, both of which are produced by human fibroblasts in culture, but our results suggest that polymorphonuclear leukocytes in diseased livers are one cellular source of circulating human hepatocyte growth factor. The immunostaining properties of biliary epithelial cells in diseased livers also suggest that the cells produce and secrete human hepatocyte growth factor.
人肝细胞生长因子已从暴发性肝衰竭患者的血浆中纯化出来，但在肝病患者的器官或细胞中该因子的产生部位尚不清楚。因此，我们使用抗人肝细胞生长因子单克隆抗体，通过免疫组化技术对3例正常肝组织和29例病变肝组织中的细胞进行染色。光学显微镜下，免疫染色的细胞因其分叶核而看似多形核白细胞。一些胆管上皮细胞也被染色。电子显微镜证实，有分叶核的免疫染色细胞是多形核白细胞，染色颗粒位于粗面内质网膜上、特异性或嗜天青颗粒周围以及细胞液中。在胆管上皮细胞中，染色颗粒偶尔见于细胞核附近粗面内质网膜的内外侧。现已知道人肝细胞生长因子与分散因子和肿瘤细胞毒因子是同一蛋白，二者均可由培养的人成纤维细胞产生，但我们的结果提示，病变肝脏中的多形核白细胞是循环中人肝细胞生长因子的一个细胞来源。病变肝脏中胆管上皮细胞的免疫染色特性也提示，这些细胞可产生并分泌人肝细胞生长因子。
