Department of Vascular Cell Biology, Max-Planck-Institute of Molecular Biomedicine, Münster, Germany.
EMBO J. 2011 Aug 19;30(20):4157-70. doi: 10.1038/emboj.2011.304.
To determine whether leukocytes need to open endothelial cell contacts during extravasation, we decided to generate mice with strongly stabilized endothelial junctions. To this end, we replaced VE-cadherin genetically by a VE-cadherin-α-catenin fusion construct. Such mice were completely resistant to the induction of vascular leaks by VEGF or histamine. Neutrophil or lymphocyte recruitment into inflamed cremaster, lung and skin were strongly inhibited in these mice, documenting the importance of the junctional route in vivo. Surprisingly, lymphocyte homing into lymph nodes was not inhibited. VE-cadherin-α-catenin associated more intensely with the actin cytoskeleton as demonstrated by its membrane mobility and detergent extractability. Our results establish the junctional route as the main pathway for extravasating leukocytes in several, although not in all tissues. Furthermore, in these tissues, plasticity of the VE-cadherin-catenin complex is central for the leukocyte diapedesis mechanism.
为了确定白细胞在渗出过程中是否需要打开内皮细胞连接，我们决定生成内皮细胞连接得到强力稳定的小鼠。为此，我们通过一个 VE-cadherin-α-catenin 融合构建体来替换 VE-cadherin。这样的小鼠完全抵抗 VEGF 或组氨酸诱导的血管渗漏。在这些小鼠中，中性粒细胞或淋巴细胞募集到炎症性精索、肺和皮肤受到强烈抑制，证明了连接途径在体内的重要性。令人惊讶的是，淋巴细胞归巢到淋巴结并没有受到抑制。如通过其膜流动性和去污剂提取性所证明的，VE-cadherin-α-catenin 与肌动蛋白细胞骨架的结合更加紧密。我们的结果确立了连接途径作为几种组织（尽管不是所有组织）中渗出白细胞的主要途径。此外，在这些组织中，VE-cadherin-catenin 复合物的可塑性对于白细胞穿胞作用机制是至关重要的。
