Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
J Gastroenterol. 2010 Mar;45(3):317-25. doi: 10.1007/s00535-009-0152-5. Epub 2009 Nov 12.
LYVE-1, a specific marker of lymphatics, is expressed in hepatic sinusoidal endothelium. A previous study revealed that LYVE-1 expression in sinusoidal endothelium was reduced in cirrhosis. However, it is still obscure how LYVE-1 expression in sinusoidal endothelium was reduced during the disease progression. To elucidate whether there were relationships among LYVE-1 attenuation, sinusoidal capillarization, and disease progression, we performed immunohistochemical investigations based on frozen human livers.
Frozen liver sections of chronic hepatitis (n = 8), cirrhosis (n = 13), and normal/control liver (n = 10) were examined by immunostaining for lymphatic endothelial markers (LYVE-1 and D2-40) and vascular endothelial markers (CD31 and von Willebrand factor). Computer-aided morphometry was applied to obtain objective data. The diseased liver tissues were also examined ultrastructurally.
In controls, sinusoidal endothelium was positive for LYVE-1 and CD31, but negative for D2-40 and von Willebrand factor. In chronic hepatitis and cirrhosis, LYVE-1 expression in sinusoidal endothelium was attenuated, especially in areas adjacent to active inflammatory or fibrotic lesions, while von Willebrand factor was reciprocally expressed in sinusoidal endothelium. The morphometric analyses revealed that LYVE-1 positivity in sinusoidal endothelium was significantly (P < 0.0001) decreased in chronic hepatitis and cirrhosis compared to controls and was negatively correlated (Rs = -0.72, P < 0.0001) to von Willebrand factor positivity. Furthermore, LYVE-1 positivity was negatively correlated to inflammatory grade (Rs = -0.51, P = 0.021) and fibrosis severity (Rs = -0.46, P = 0.038). Sinusoidal endothelium in the diseased livers showing LYVE-1 attenuation had lost fenestrations.
These findings indicated that LYVE-1 attenuation in sinusoidal endothelium was one of the manifestations of capillarization, and was associated with hepatic disease progression.
LYVE-1 是淋巴管的特异性标志物，表达于肝窦内皮细胞。先前的研究表明，肝硬化时肝窦内皮细胞的 LYVE-1 表达减少。然而，在疾病进展过程中，肝窦内皮细胞的 LYVE-1 表达如何减少仍不清楚。为了阐明 LYVE-1 衰减、窦状隙毛细血管化和疾病进展之间是否存在关系，我们基于冷冻人肝组织进行了免疫组织化学研究。
通过免疫组织化学染色检测淋巴管内皮标志物（LYVE-1 和 D2-40）和血管内皮标志物（CD31 和血管性血友病因子），对慢性肝炎（n=8）、肝硬化（n=13）和正常/对照肝（n=10）的冷冻肝切片进行了检查。应用计算机辅助形态计量学获取客观数据。还对病变肝组织进行了超微结构检查。
在对照组中，肝窦内皮细胞表达 LYVE-1 和 CD31，但不表达 D2-40 和血管性血友病因子。在慢性肝炎和肝硬化中，肝窦内皮细胞的 LYVE-1 表达减弱，尤其是在与活跃炎症或纤维化病变相邻的区域，而血管性血友病因子则在肝窦内皮细胞中呈反向表达。形态计量学分析显示，与对照组相比，慢性肝炎和肝硬化中肝窦内皮细胞的 LYVE-1 阳性率显著降低（P＜0.0001），且与血管性血友病因子阳性率呈负相关（Rs=-0.72，P＜0.0001）。此外，LYVE-1 阳性率与炎症分级（Rs=-0.51，P=0.021）和纤维化严重程度（Rs=-0.46，P=0.038）呈负相关。在表现出 LYVE-1 衰减的病变肝窦内皮细胞中，失去了窗孔。
这些发现表明，肝窦内皮细胞的 LYVE-1 衰减是毛细血管化的表现之一，与肝疾病进展有关。
