Stages of extravasation of a leukocyte. (A) Leukocytes first undergo tethering and rolling on the endothelium, mediated by E-selectin, L-selectin, and P-selectin and their carbohydrate ligands. Activation and adhesion: leukocyte rolling facilitates interaction with chemoattractants present on endothelial surfaces, which in turn causes leukocyte activation that triggers firm adhesion and arrest, mediated by the integrins macrophage-1 (Mac-1), leukocyte function antigen-1 (LFA-1) and very late antigen-4 (VLA-4) binding to their endothelial ligands intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Subsequently, leukocytes engage in lateral migration over the endothelial wall in search of a site to transmigrate, guided by VCAM-1/ICAM-1-enriched transmigratory cups (asterisks in (B) and (C)), present on endothelial cells. The last step in this cascade is transendothelial migration or diapedesis, whereby the leukocytes cross the endothelial barrier, either (B) paracellular, through the interendothelial junctions, or (C) transcellular, via the formation of a transcellular pore. See [7–9, 13] for additional details.