Figure 2.

Leukocyte diapedesis through or between endothelial cells. (a) The initiation of paracellular and transcellular transmigration is believed to involve distinct molecular mechanisms that allow transient endothelial permeability to leukocytes. Destabilization of VE-cadherin based cell-cell contacts is recognized as the major mechanisms that initiates the opening of the paracellular pathway. It is thought that leukocytes trigger rapid dephosphorylation of Tyr731 via the tyrosine phosphatase SHP-2 allowing the adaptin AP-2 to bind and initiate endocytosis of VE-cadherin and thereby destabilize VE-cadherin based junctions. (b) The initiation of a transcellular passageway is thought to occur through fusion of ICAM-1 bearing endocytic vesicles forcing a transcellular pore allowing transcellular migration to occur. For both transmigration routes, endothelial pore opening is in part mediated by mechanical forces that are generated by migrating leukocytes. Polarized actin polymerization in the leukocyte elicits pulling and pushing forces that supports their movement through the confined endothelial pore.