Muller William A
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Immunol Rev. 2016 Sep;273(1):61-75. doi: 10.1111/imr.12443.
Transendothelial migration (TEM) of polymorphonuclear leukocytes (PMN) involves a carefully orchestrated dialog of adhesion and signaling events between leukocyte and endothelial cell. This article focuses on the contribution of endothelial cells to transmigration. The initiation of TEM itself generally requires interaction of PECAM on the leukocyte with PECAM at the endothelial cell border. This is responsible for the transient elevation of cytosolic-free calcium ions in endothelium that is required for TEM and for recruitment of membrane from the lateral border recycling compartment (LBRC). TEM requires LBRC to move to the site at which TEM will take place and for VE-cadherin to move away. Targeting of the LBRC to this site likely precedes movement of VE-cadherin and may play a role in clearing VE-cadherin from the site of TEM. The process of TEM can be dissected into steps mediated by distinct pairs of PMN/endothelial interacting molecules. CD99 regulates a step at or close to the end of TEM. CD99 signals through soluble adenylyl cyclase to activate PKA to trigger ongoing targeted recycling of the LBRC. Paracellular transmigration predominates (≥90% of events) in the cremaster muscle circulation, but transcellular migration may be more important at sites such as the blood-brain barrier. Both processes involve many of the same molecules and recruitment of the LBRC.
多形核白细胞（PMN）的跨内皮迁移（TEM）涉及白细胞与内皮细胞之间精心编排的粘附和信号事件对话。本文重点关注内皮细胞对迁移的贡献。TEM的起始通常需要白细胞上的PECAM与内皮细胞边界处的PECAM相互作用。这导致内皮细胞中游离钙离子的短暂升高，这是TEM以及从侧向边界回收区室（LBRC）募集膜所必需的。TEM需要LBRC移动到TEM发生的部位，并使VE-钙粘蛋白移开。LBRC靶向该部位可能先于VE-钙粘蛋白的移动，并可能在从TEM部位清除VE-钙粘蛋白中发挥作用。TEM过程可分解为由不同对的PMN/内皮相互作用分子介导的步骤。CD99调节TEM接近尾声或结束时的一个步骤。CD99通过可溶性腺苷酸环化酶发出信号，激活PKA以触发LBRC持续的靶向回收。在提睾肌循环中，旁细胞迁移占主导（≥90%的事件），但在血脑屏障等部位，穿细胞迁移可能更重要。这两个过程都涉及许多相同的分子和LBRC的募集。
