美国西北大学范伯格医学院William A. Muller研究组发现，通过血小板内皮细胞粘附分子1 (PECAM, PECAM-1, CD31)的机械转导启动迁移，并揭示了血管内皮生长因子受体2 (VEGFR2)在迁移中的作用。2023年8月28日，国际知名学术期刊《免疫》发表了这一成果。

他们使用荧光寿命成像显微镜(FLIM)显示，TEM期间对内皮PECAM的物理牵引启动了内皮信号通路。在这种作用下，内皮PECAM作为VE-钙粘蛋白和VEGFR2的机械转导复合物的一部分，这预示着有效的TEM需要VEGFR2。他们发现TEM需要VEGFR2及其Y1175的磷酸化能力，但不需要VEGF或VEGFR2内源性激酶活性。

他们使用可诱导的内皮特异性VEGFR2缺陷小鼠，在三种小鼠炎症模型中发现，内皮细胞VEGFR2缺失通过选择性阻断渗出显著(≥75%)减少中性粒细胞外渗。这些发现提供了对转运过程更完整的理解，并确定了几个潜在的抗炎靶点。

据介绍，CD31在白细胞假足上与内皮细胞边界的PECAM结合，可启动跨内皮迁移(TEM, diapedesis)。

附：英文原文

Title: Mechanotransduction via endothelial adhesion molecule CD31 initiates transmigration and reveals a role for VEGFR2 in diapedesis

Author: Tao Fu, David P. Sullivan, Annette M. Gonzalez, Maureen E. Haynes, Prarthana J. Dalal, Nakisha S. Rutledge, Abigail L. Tierney, Julia A. Yescas, Evan W. Weber, William A. Muller

Issue&Volume: 2023-08-28

Abstract: Engagement of platelet endothelial cell adhesion molecule 1 (PECAM, PECAM-1, CD31)on the leukocyte pseudopod with PECAM at the endothelial cell border initiates transendothelialmigration (TEM, diapedesis). We show, using fluorescence lifetime imaging microscopy(FLIM), that physical traction on endothelial PECAM during TEM initiated the endothelialsignaling pathway. In this role, endothelial PECAM acted as part of a mechanotransductioncomplex with VE-cadherin and vascular endothelial growth factor receptor 2 (VEGFR2),and this predicted that VEGFR2 was required for efficient TEM. We show that TEM requiredboth VEGFR2 and the ability of its Y1175 to be phosphorylated, but not VEGF or VEGFR2endogenous kinase activity. Using inducible endothelial-specific VEGFR2-deficientmice, we show in three mouse models of inflammation that the absence of endothelialVEGFR2 significantly (by ≥75%) reduced neutrophil extravasation by selectively blockingdiapedesis. These findings provide a more complete understanding of the process oftransmigration and identify several potential anti-inflammatory targets.

DOI: 10.1016/j.immuni.2023.08.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00357-6