Circulating leukocytes migrate to injured tissue directed by adhesion molecules. The initial step, rolling, is mediated by selectins on leukocytes (L-selectin) and endothelium (P- and E-selectin). The rolling leukocytes are exposed to tissue-derived chemokines. These upregulate the avidity of integrins, which mediate the firm adhesion of cells to endothelium by interacting with immunoglobulin superfamily members such as intercellular adhesion molecule–1. Finally, the cells migrate through the vessel wall, directed by platelet-endothelial cell adhesion molecule-1 and other immunoglobulin ligands. Interruption of this cascade can block immunocyte extravasation.