van Buul Jaap D, Hordijk Peter L
Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands.
Arterioscler Thromb Vasc Biol. 2004 May;24(5):824-33. doi: 10.1161/01.ATV.0000122854.76267.5c. Epub 2004 Feb 19.
Under a variety of (patho) physiological conditions, leukocytes will leave the bloodstream by crossing the endothelial monolayer that lines the vessels and migrate into the underlying tissues. It is now clear that the process of extravasation involves a range of adhesion molecules on both leukocytes and endothelial cells, as well as extensive intracellular signaling that drives adhesion and chemotaxis on the one hand and controls a transient modulation of endothelial integrity on the other. We review here the current knowledge of the intracellular signaling pathways that are activated in the context of transendothelial migration in leukocytes and in endothelial cells. In leukocytes, polarization of receptors and of the signaling machinery is of key importance to drive adhesion and directional migration. Subsequent adhesion-induced signaling in endothelial cells, mediated by Rho-like GTPases and reactive oxygen species, induces a transient and focal loss of endothelial cell-cell adhesion to allow transmigration of the leukocyte. This review underscores the notion that we have likely just scratched the surface in revealing the complexity of the signaling that controls leukocyte transendothelial migration.
在多种（病理）生理条件下，白细胞会穿过血管内衬的内皮单层细胞离开血流，并迁移到下方组织中。现在已经清楚，外渗过程涉及白细胞和内皮细胞上的一系列黏附分子，以及一方面驱动黏附和趋化作用、另一方面控制内皮完整性短暂调节的广泛细胞内信号传导。我们在此回顾目前关于在白细胞和内皮细胞跨内皮迁移过程中被激活的细胞内信号通路的知识。在白细胞中，受体和信号传导机制的极化对于驱动黏附和定向迁移至关重要。随后，由类Rho GTP酶和活性氧介导的内皮细胞中黏附诱导信号传导，会诱导内皮细胞间黏附的短暂局部丧失，以允许白细胞迁移。这篇综述强调了这样一种观念，即在揭示控制白细胞跨内皮迁移的信号传导复杂性方面，我们可能只是触及了表面。
