The role of endothelial cell-selective adhesion molecule (ESAM) in neutrophil emigration into inflamed tissues

Abstract

Leukocyte emigration into inflamed tissues is among the most intensely pursued topics in the field of inflammation. Research focuses on the molecular factors activating endothelial cells and leukocytes, the adhesive molecules facilitating the contact between both cell types and the mechanisms allowing leukocytes to transmigrate through the blood vessel endothelium. In the last few years, studies have been intensified to understand how leukocytes, once captured to the vessel wall overcome the barrier made of endothelial cells linked to each other by interendothelial junctions. The mechanisms by which these leukocytes traverse the endothelial cell layer to reach the underlying tissue, a process called diapedesis, are largely unknown. Whereas convincing evidence has been published that polymorphonuclear leukocytes (PMN) can indeed migrate through endothelial cells in a transcellular fashion in vivo [1] as well as in vitro [2], careful quantitative analysis has demonstrated that at least in vitro the majority of PMNs and other leukocytes migrate via a paracellular route through the contact areas between endothelial cells [2, 3]. Consequently, a number of endothelial cell contact proteins such as PECAM-1, members of the junctional adhesion molecule family (JAM-A, -B and -C), CD99 and ICAM-2 have been reported to support leukocyte extravasation [4–7] . PECAM-1 was the first of these proteins that was identified in the context of leukocyte extravasation [8]. Its relevance for neutrophil extravasation is well established [9]. Although PECAM-1, JAM-A and ICAM-2 were shown by intravital microscopy to be involved in the transmigration process in vivo, the detailed molecular mechanism by which they participate in the process is still unknown.