Figure 1. The multi-step paradigm of cellular trafficking.

The critical first step for all vascular emigration is the deceleration of blood-borne cells on the endothelial surface, a process mediated by selectins and their ligands (step 1). The common minimal binding determinant for all three selectins is the tetrasaccharide sialyl-Lewis x (sLe^x). Rolling is necessary for the cells to ‘taste’ the local milieu, i.e., to interact with locally produced chemotactic stimuli. Successful chemokine signaling results in activation of integrins (step 2), which results in firm adhesion (step 3) and finally, transendothelial migration (step 4).