Endothelial signaling in leukocyte transmigration

Leukocyte transendothelial migration is a multistep process coordinated by chemokine receptors, integrins and cell adhesion molecules. The interaction between leukocytes and endothelial cells is accompanied by bidirectional signaling in both cell types, which is initiated following formation of specialized, "docking" structures. In recent years, it has become clear that signaling in the endothelial cells importantly contributes to the transmigration process. This signaling induces a focal and transient loss of endothelial cell-cell adhesion, which is dependent on vascular-endothelial cadherin. Recent work from several groups has implicated Rho-like GTPases, reactive oxygen species, changes in the actin cytoskeleton and protein tyrosine phosphorylation in the control of VE-cadherin and associated proteins. This review discusses what is currently known about control of VE-cadherin function via intracellular signaling, and its induction by endothelial adhesion molecules of the immunoglobulin superfamily.