title: Recent insights into endothelial control of leukocyte extravasation.
abstract: In the process of leukocyte migration from the circulation across the vascular wall, the crosstalk with endothelial cells that line the blood vessels is essential. It is now firmly established that in endothelial cells important signaling events are initiated upon leukocyte adhesion that impinge on the regulation of cell-cell contact and control the efficiency of transendothelial migration. In addition, several external factors such as shear force and vascular stiffness were recently identified as important regulators of endothelial signaling and, consequently, leukocyte transmigration. Here, I review recent insights into endothelial signaling events that are linked to leukocyte migration across the vessel wall. In this field, protein phosphorylation and Rho-mediated cytoskeletal dynamics are still widely studied using increasingly sophisticated mouse models. In addition, activation of tyrosine phosphatases, changes in endothelial cell stiffness as well as different vascular beds have all been established as important factors in endothelial signaling and leukocyte transmigration. Finally, I address less-well-studied but interesting components in the endothelium that also control transendothelial migration, such as the ephrins and their Eph receptors, that provide novel insights in the complexity associated with this process.
authors.affiliation: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Swammerdam Institute for Life Sciences, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands. p.hordijk@sanquin.nl.|Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands. p.hordijk@sanquin.nl.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Hordijk
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D059289:Vascular Stiffness / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins
keywords: Mechanosignaling; Rho GTPases; Tyrosine phosphorylation; VE-cadherin