Purpose

Transport of water and solutes across vascular endothelium is important in normal physiology and critical in the development of various diseases, including atherosclerosis. However, there is debate about the routes for such transport. We recently showed that an albumin-sized tracer crossed endothelium at bicellular and tricellular junctions, a tracer having the size of high density lipoprotein crossed only through tricellular junctions, and a tracer with the size of low density lipoprotein was unable to cross by either route and instead traversed the cells themselves. Here we review previous work on the structure and function of tricellular junctions. We then describe a study in which we assessed the role of such junctions in the transport of an albumin-sized tracer.

Methods

We examined normal endothelial monolayers, the effect of agonists that modify their permeability, and the influence of different patterns of shear stress.

Results

Under normal conditions, approximately 85% of transendothelial transport occurred through tricellular junctions. This fraction was unchanged when permeability was reduced by sphingosine-1-phosphate or increased by thrombin, and also did not differ between endothelium exposed to multidirectional as opposed to uniaxial shear stress despite a > 50% difference in permeability.

Conclusion

These data show that tricellular junctions dominate normal transport of this tracer and largely determine influences of agonists and shear. The effects were attributable to changes in both the number and conductivity of the junctions. Further investigation of these structures will lead to increased understanding of endothelial barrier function and may suggest new therapeutic strategies in disease.

中文翻译：

---

三细胞连接在大分子跨内皮运输中的作用。

 目的

水和溶质穿过血管内皮的运输对于正常生理学很重要，并且对于包括动脉粥样硬化在内的各种疾病的发展至关重要。然而，对于这种运输的路线存在争议。我们最近表明，白蛋白大小的示踪剂在双细胞和三细胞连接处穿过内皮，具有高密度脂蛋白大小的示踪剂仅通过三细胞连接交叉，而具有低密度脂蛋白大小的示踪剂无法通过任何一种途径穿过，并且相反，它遍历了细胞本身。在这里，我们回顾了先前关于三细胞连接的结构和功能的工作。然后，我们描述了一项研究，其中我们评估了此类连接在白蛋白大小的示踪剂运输中的作用。

 方法

我们检查了正常的内皮单层、改变其渗透性的激动剂的作用以及不同剪切应力模式的影响。

 结果

正常情况下，大约 85% 的跨内皮转运通过三细胞连接发生。当 1-磷酸鞘氨醇降低通透性或凝血酶增加通透性时，该分数没有变化，并且尽管通透性差异 > 50%，但暴露于多向剪应力与单轴剪切应力的内皮之间也没有差异。

 结论

这些数据表明，三细胞连接主导着该示踪剂的正常运输，并在很大程度上决定了激动剂和剪切力的影响。这种影响可归因于结点数量和电导率的变化。对这些结构的进一步研究将加深对内皮屏障功能的了解，并可能提出新的疾病治疗策略。