Vainionpää Noora, Bützow Ralf, Hukkanen Mika, Jackson David G, Pihlajaniemi Taina, Sakai Lynn Y, Virtanen Ismo
Institute of Biomedicine/Anatomy, University of Helsinki, Haartmaninkatu 8, FI-00014, Helsinki, Finland.
Cell Tissue Res. 2007 May;328(2):317-28. doi: 10.1007/s00441-006-0366-2. Epub 2007 Jan 30.
The endothelial cells of blood vessels assemble basement membranes that play a role in vessel formation, maintenance and function, and in the migration of inflammatory cells. However, little is known about the distribution of basement membrane constituents in lymphatic vessels. We studied the distribution of basement membrane proteins in lymphatic vessels of normal human skin, digestive tract, ovary and, as an example of tumours with abundant lymphatics, ovarian carcinomas. Basement membrane proteins were localized by immunohistochemistry with monoclonal antibodies, whereas lymphatic capillaries were detected with antibodies to the lymphatic vessel endothelial hyaluronan receptor-1, LYVE-1. In skin and ovary, fibrillar immunoreactivity for the laminin alpha4, beta1, beta2 and gamma1 chains, type IV and XVIII collagens and nidogen-1 was found in the basement membrane region of the lymphatic endothelium, whereas also heterogeneous reactivity for the laminin alpha5 chain was detected in the digestive tract. Among ovarian carcinomas, intratumoural lymphatic vessels were found especially in endometrioid carcinomas. In addition to the laminin alpha4, beta1, beta2 and gamma1 chains, type IV and XVIII collagens and nidogen-1, carcinoma lymphatics showed immunoreactivity for the laminin alpha5 chain and Lutheran glycoprotein, a receptor for the laminin alpha5 chain. In normal lymphatic capillaries, the presence of primarily alpha4 chain laminins may therefore compromise the formation of endothelial basement membrane, as these truncated laminins lack one of the three arms required for efficient network assembly. The localization of basement membrane proteins adjacent to lymphatic endothelia suggests a role for these proteins in lymphatic vessels. The distribution of the laminin alpha5 chain and Lutheran glycoprotein proposes a difference between normal and carcinoma lymphatic capillaries.
血管内皮细胞组装基底膜,基底膜在血管形成、维持和功能以及炎症细胞迁移中发挥作用。然而,关于基底膜成分在淋巴管中的分布却知之甚少。我们研究了基底膜蛋白在正常人体皮肤、消化道、卵巢淋巴管中的分布,并以淋巴管丰富的肿瘤——卵巢癌为例进行了研究。采用单克隆抗体通过免疫组织化学法定位基底膜蛋白,而用抗淋巴管内皮透明质酸受体-1(LYVE-1)抗体检测淋巴管。在皮肤和卵巢中,在淋巴管内皮的基底膜区域发现了层粘连蛋白α4、β1、β2和γ1链、IV型和XVIII型胶原以及巢蛋白-1的纤维状免疫反应性,而在消化道中也检测到了层粘连蛋白α5链的异质性反应。在卵巢癌中,肿瘤内淋巴管尤其见于子宫内膜样癌。除了层粘连蛋白α4、β1、β2和γ1链、IV型和XVIII型胶原以及巢蛋白-1外,癌淋巴管还显示出对层粘连蛋白α5链和路德糖蛋白(层粘连蛋白α5链的受体)的免疫反应性。因此,在正常淋巴管中,主要是α4链层粘连蛋白的存在可能会损害内皮基底膜的形成,因为这些截短的层粘连蛋白缺乏有效网络组装所需的三条臂之一。基底膜蛋白在淋巴管内皮附近的定位表明这些蛋白在淋巴管中发挥作用。层粘连蛋白α5链和路德糖蛋白的分布表明正常和癌性淋巴管之间存在差异。