Vitronectin in the cirrhotic liver: An immunomarker of mature fibrosis

Vitronectin in the cirrhotic liver: An immunomarker of mature fibrosis
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DOI:
10.1053/hupa.2001.29675
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发表时间:
2001-12-01
期刊:
影响因子:
3.3
通讯作者:
Gould, VE
Gould, VE
中科院分区:
医学3区
文献类型:
--
作者:
Koukoulis, GK;Shen, JK;Gould, VE

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玻连蛋白(Vitronectin,Vn)是由肝细胞产生的一种多功能血浆糖蛋白。VN作为一种细胞粘附分子已被广泛研究。然而,其在肝细胞外基质中的定位受到的关注相对较少。用抗生物素蛋白-生物素复合物法对5例正常肝组织和20例肝炎后肝硬化组织的冰冻切片进行了染色。半定量评估免疫染色的程度和强度(0,无染色; 1+,弱局灶性染色; 2+,强局灶性染色; 3+,强弥漫性染色)。石蜡切片用Masson三色法(NIT)和Shikata地衣红法(Or)染色。通过Western印迹法分析来自选定病例的冷冻样品。在正常肝脏中,3+染色仅限于门静脉血管。汇管区结缔组织显示极轻微染色(0至1+)。肝硬化隔呈强染色(2+)。如NIT和Or染色所示,缺乏显著炎症且由致密结缔组织组成的隔膜显示出最强的Vn反应(3+)。免疫印迹数据强烈相关的Vn增加,在急性肝硬化。Vn免疫反应性显着增加,在肝硬化的基质,无论记录减少血浆Vn。与胶原蛋白、弹性蛋白和蛋白聚糖的结合是目前Vn在组织中沉积的有利机制。先前的研究表明,在糖尿病患者中,血浆Vn与胶原蛋白的亲和力增加。Vn在老化皮肤中也增加,与真皮弹性纤维相关。在其他组织中,Vn沉积反映了损伤的慢性性。因此,肝脏中的Vn免疫反应性可以被认为是纤维化的标志物,特别是慢性/成熟纤维化的标志物,这与先前对动脉间隔的增强地衣红染色的观察结果相似。用Vn和腱生蛋白(一种持续重塑或最近形成的纤维组织的标志物)对活检标本进行免疫标记可能有助于诊断。Copyright(C)2001 by W.B.桑德斯公司
Vitronectin (Vn) is a multifunctional plasma glycoprotein produced by hepatocytes. Vn has been studied extensively as a cell adhesion molecule. However, its localization in the hepatic extracellular matrix has received relatively little attention. Cryosections of 5 normal liver samples and of 20 specimens showing posthepatitic cirrhosis were stained by the avidin-biotin complex method with a well-characterized monoclonal antibody to Vn. The extent and intensity of immunostaining were assessed semiquantitatively (0, no staining; 1+, weak focal staining; 2+, strong focal staining; 3+, strong diffuse staining). Paraffin sections from the same samples were stained with Masson trichrome (NIT) and Shikata orcein (Or) methods. Frozen samples from selected cases were analyzed by Western blotting. In the normal liver, 3+ staining was limited to portal vessels. The portal tract connective tissue showed minimal staining (0 to 1+). Cirrhotic septa showed strong staining (2+). Septa lacking significant inflammation and composed of dense connective tissue, as indicated by NIT and Or stains, showed the strongest Vn reactions (3+). Immunoblotting data strongly correlated with Vn increase in cirrhotic livers. Vn immunoreactivity is markedly increased in the cirrhotic liver matrix, regardless of the documented decrease in plasma Vn. Binding to collagen, elastin, and proteoglycans is die current favored mechanism of Vn deposition in tissues. Previous studies in cirrhotic patients showed increased affinity of plasma Vn to collagen. Vn is also increased in aged skin, associated with dermal elastic fibers. In other tissues, Vn deposition reflects chronicity of injury. Therefore, Vn immunoreactivity in liver can be considered a marker of fibrosis, especially of chronic/mature fibrosis, paralleling previous observations on enhanced orcein staining of cirrhotic septa. Immunolabeling of biopsy specimens with Vn and tenascin, a marker of ongoing remodeling or recently formed fibrous tissue, could be diagnostically helpful. Copyright (C) 2001 by W.B. Saunders Company.