Leach L, Lammiman M J, Babawale M O, Hobson S A, Bromilou B, Lovat S, Simmonds M J
School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, UK.
Placenta. 2000 Jul-Aug;21(5-6):547-57. doi: 10.1053/plac.2000.0541.
Tight and adherens junctions are major determinants of endothelial integrity. Molecules present therein have been implicated in vascular permeability, stability of junctions, angiogenesis and intracellular signalling. Using immunofluorescence and confocal scanning microscopy, the adherens junctions (AJs) in human placental vessels were found to contain the entire cadherin-catenin complex predicted from in vitro studies. Vascular endothelial cadherin (VE-cadherin) clusters were co-localized with beta-catenin, an important signal transduction ligand, and with alpha-catenin, which is thought to link the complex to the peri-junctional actin. Antibodies to plakoglobin, a molecule shown to be a component of stable adherens junctions, revealed immunoreactivity in clefts of stromal villous vessels, but weak or negative immunoreactivity in intermediate and terminal villi. Tight junctional molecules demonstrated a differential surface expression. Within the same villous tree, arteries, veins and arterioles contained occludin but the exchange vessels in terminal villi were immunonegative. ZO-1, however, was present throughout. Ultrastructurally, there were no differences in frequency, position or dimension of tight junctions in these vessels. They showed a consistent 4 nm separation between outer membrane leaflets regardless of their location in the vascular tree. Occludin is not necessary for formation of tight junctions in the placenta; it may have an accessory role providing stability or added adhesiveness to tight junctions of large vessels. Its absence in terminal villous microvessels, along with the weak plakoglobin immunoreactivity in AJs, suggest that the junctions here are less stable. This may allow the increased plasticity necessary in terminal villi for continual growth, proliferation and solute exchange.
紧密连接和黏附连接是内皮完整性的主要决定因素。其中存在的分子与血管通透性、连接稳定性、血管生成和细胞内信号传导有关。利用免疫荧光和共聚焦扫描显微镜，发现人胎盘血管中的黏附连接（AJs）包含体外研究预测的完整钙黏蛋白-连环蛋白复合体。血管内皮钙黏蛋白（VE-钙黏蛋白）簇与重要的信号转导配体β-连环蛋白以及被认为将该复合体与连接周围肌动蛋白相连的α-连环蛋白共定位。针对桥粒斑珠蛋白（一种被证明是稳定黏附连接成分的分子）的抗体，在基质绒毛血管的裂隙中显示出免疫反应性，但在中间绒毛和终末绒毛中免疫反应性较弱或为阴性。紧密连接分子表现出不同的表面表达。在同一绒毛树内，动脉、静脉和小动脉含有闭合蛋白，但终末绒毛中的交换血管免疫阴性。然而，ZO-1在各处均有表达。在超微结构上，这些血管中紧密连接的频率、位置或尺寸没有差异。无论其在血管树中的位置如何，它们在外膜小叶之间均显示出一致的4nm间距。闭合蛋白对于胎盘紧密连接的形成并非必需；它可能具有辅助作用，为大血管的紧密连接提供稳定性或增加黏附性。其在终末绒毛微血管中的缺失，以及AJs中桥粒斑珠蛋白免疫反应性较弱，表明此处的连接不太稳定。这可能允许终末绒毛中持续生长、增殖和溶质交换所需的更大可塑性。
