Adhesion Molecules of Leukocyte Trafficking :
Molecular Basis of Leukocyte Transmigration

Leukocyte transmigrates across the endothelium via the endothelial cell junctions. The endothelial junctions are stabilized by the tight junctions and the adherens junctions. Both types of supramolecular structures are present throughout the body with tight junctions being prevalent in areas where barrier maintenance is critical and adherens junctions in areas such as the high endothelial venuoles, where there is a high rate of leukocyte transmigration. The main components of the tight junction are the occludins, claudins, JAM-A, B, and C. The adherens junctions are stabilized by the vascular endothelial (VE)-cadherins, which are associated to the actin cytoskeleton via the catenins, platelet endothelial cellular adhesion molecule-1 (PECAM-1, CD31) and CD99.

The molecular processes associated with transmigration are sufficiently complex as they involve not only the binding events between the leukocyte and the endothelial cell, but also the disruption of the endothelial junction. An important early event in transmigration is the binding of LFA-1 to JAM-A. This is followed by homophilic interactions between JAM-A, PECAM-1 and CD-99. Subsequent interactions between PECAM-1 and a v b 3 , allow the cell to leave the endothelial junction ( Schenkel et al., 2004) . JAM-B and JAM-C have also been implicated in some of the later events of transmigration.

Inflammation leads to a number of changes that occur at the junction in order for leukocyte transmigration to be possible. The breakdown and internalization of the VE-cadherin complexes is mediated by protease calpain or, in the case of neutrophil transmigration, the neutrophil elastase enzyme. Inflammation is also associated with redistribution of PECAM-1 and JAM-A to assist in the recruitment of leukocytes to the junction.