Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node
Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node
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DOI：
10.1002/eji.200838140
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发表时间：
2008-08-01
影响因子：
5.4
通讯作者：
Engelhardt, Britta
中科院分区：
文献类型：
--
作者：
Pfeiffer, Friederike;Kumar, Varsha;Engelhardt, Britta
淋巴结战略性地定位于血液和淋巴血管系统之间的界面，将免疫细胞和抗原输送到淋巴结。由于内皮细胞的细胞连接积极调节血管通透性和细胞交通，我们通过对粘附分子和紧密连接分子进行广泛的免疫荧光研究，研究了它们的分子组成，包括血管内皮(VE)-cadherin、血管粘附蛋白1、3、5和12、occludin、连接粘附分子家族成员和内皮细胞选择性粘附分子(ESAM)-1、血小板内皮细胞粘附分子-1、ZO-1和ZO-2。我们发现，作为初始淋巴细胞进入位点的高内皮小静脉（HEV）的连接是独特的，因为它们缺乏内皮细胞特异性的claudin-5。LYVE-1（+）窦壁内皮细胞为到达传入淋巴的可溶性分子形成扩散屏障，并利用claudin-5和ESAM-1建立特特性紧密连接。不同血管室之间的空间关系分析显示，HEV延伸到皮层外的髓窦，在那里它们受到窦壁内皮细胞的保护，避免与淋巴直接接触。外周淋巴结的血液和淋巴管内皮中存在的细胞连接的特定分子结构建立了控制抗原和免疫细胞在该组织内分布的独特屏障。
Lymph nodes are strategically localized at the interfaces between the blood and lymphatic vascular system, delivering immune cells and antigens to the lymph node. As cellular junctions of endothelial cells actively regulate vascular permeability and cell traffic, we have investigated their molecular composition by performing an extensive immunofluorescence study for adherens and tight junction molecules, including vascular endothelium (VE)-cadherin, the vascular claudins 1, 3, 5 and 12, occludin, members of the junctional adhesion molecule family plus endothelial cell-selective adhesion molecule (ESAM)-1, platelet endothelial cell adhesion molecule-1, ZO-1 and ZO-2. We found that junctions of high endothelial venules (HEV), which serve as entry site for naive lymphocytes, are unique due to their lack of the endothelial cell-specific claudin-5. LYVE-1(+) sinus-lining endothelial cells form a diffusion barrier for soluble molecules that arrive at the afferent lymph and use claudin-5 and ESAM-1 to establish characteristic tight junctions. Analysis of the spatial relationship between the different vascular compartments revealed that HEV extend beyond the paracortex into the medullary sinuses, where they are protected from direct contact with the lymph by sinus-lining endothelial cells. The specific molecular architecture of cellular junctions present in blood and lymphatic vessel endothelium in peripheral lymph nodes establishes distinct barriers controlling the distribution of antigens and immune cells within this tissue.