Adhesion and signaling molecules controlling the transmigration of leukocytes through endothelium

Abstract

Migration of leukocytes into tissue is a key element of innate and adaptive immunity. While the capturing of leukocytes to the blood vessel wall is well understood, little is known about the mechanisms underlying the actual transmigration of leukocytes through the vessel wall (diapedesis). Even a basic question such as whether leukocytes migrate through openings between adjacent endothelial cells (junctional pathway) or through single endothelial cells (transcellular pathway) is still a matter of intensive debate. It is generally accepted that both pathways exist; however, whether they are of equal physiological significance is unclear. Several endothelial adhesion and signaling molecules have been identified, most of them at endothelial cell contacts, which participate in leukocyte diapedesis. A concept is evolving suggesting that transendothelial migration of leukocytes is a stepwise process. Blocking or eliminating some of the different adhesion and signaling proteins results in very different effects, such as trapping of leukocytes above endothelial cell contacts, in between endothelial cells, or between the endothelium and the underlying basement membrane. Other proteins are involved in the opening of endothelial cell contacts and yet others in their maintenance providing the barrier for extravasating leukocytes. The various molecular players and the functional steps involved in diapedesis are discussed.

The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

“…Because this suggested that the expression of L1 is regulated by tumor-or infl ammatory cell -derived fac- heterophilic binding partners of L1 involved in DC -EC interactions remain elusive, members of the integrin family are suitable candidates. Indeed, the cross talk between integrins and Ig-like CAMs, such as members of the ICAM and JAM families, is a key step during leukocyte transmigration ( 28 ). In support of this hypothesis, not only has L1 been reported to interact with integrins in other experimental systems ( 10,29,30 ) but L1 homophilic binding upon cell-cell adhesion has been shown to promote integrin recruitment and activation ( 31 ).…”

Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response

“…Here, membrane-bound receptors and their cognate ligands may play essential roles (Gomez-Rodriguez et al, 2007;Huang et al, 1999;Hwang and Ki, 2011;Hwang et al, 2000;Peterson, 2003;Vestweber, 2007). The set of receptors and ligands making contact with each other in cells determine the phenotypic changes in those cells during or after the contact.…”

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

“…The activation of endothelial cells increases vascular permeability, initiates inflammatory responses, and recruits leukocytes by the upregulation of the leukocyte adhesion molecules ICAM1, vascular cell adhesion molecule 1 (VCAM1), and E-selectin (41). ICAM1 is minimally expressed on resting endothelial cells and is upregulated in response to inflammatory mediators, such as virus infection and the proinflammatory cytokines IL-1␤, IL-6, and TNF-␣ (31,38).…”