Most impoant for diapedisis

Ref Robbins 8/e p50;9/e p77 Leukocytes normally flow rapidly in the blood, and in inflamma- tion, they have to be stopped and brought to the offending agent or the site of tissue damage, which are typically outside the vessels. The sequence of events in the recruitment of leuko- cytes from the vascular lumen to the extravascular space consists of (1) margination and rolling along the vessel wall; (2) firm adhesion to the endothelium; (3) transmigra- tion between endothelial cells; and (4) migration in inter- stitial tissues toward a chemotactic stimulus (Fig. 2-5). Rolling, adhesion, and transmigration are mediated by the interactions of adhesion molecules on leukocytes and endothelial surfaces (see later on). Chemical mediators-- chemoattractants and ceain cytokines--affect these pro- cesses by modulating the surface expression and binding affinity of the adhesion molecules and by stimulating direc- tional movement of the leukocytes. Margination and Rolling. As blood flows from capillaries into postcapillary venules, circulating cells are swept by laminar flow against the vessel wall. Because the smaller red cells tend to move faster than the larger white cells, leukocytes are pushed out of the central axial column and thus have a better oppounity to interact with lining endothelial cells, especially as stasis sets in. This process of leukocyte accumulation at the periphery of vessels is called margination. If the endothelial cells are activated by cytokines and other mediators produced locally, they express adhesion molecules to which the leukocytes attach loosely. These cells bind and detach and thus begin to tumble on the endothelial surface, a process called rolling. Adhesion. The rolling leukocytes are able to sense changes in the endothelium that initiate the next step in the reaction of leukocytes, which is firm adhesion to endothelial sur- faces. This adhesion is mediated by integrins expressed on leukocyte cell surfaces interacting with their ligands on endothelial cells