Adhesion molecule cascades direct lymphocyte recirculation and leukocyte migration during inflammation

Leukocyte interactions with vascular endothelium are highly orchestrated pr ocesses that include the capture of free-flowing leukocytes from the blood with subsequent leukocyte rolling, arrest, firm adhesion, and ensuing diape desis. These interactions occur under high shear stresses within venules an d depend on multiple families of adhesion molecules. Many of the adhesion m olecules involved are now identified. In addition, precise mechanisms under lying their regulation and our understanding of how different families of a dhesion molecules work together is becoming clearer. Specifically, leukocyt e/endothelial cell interactions such as capture, rolling, and firm adhesion can no longer be viewed as occurring in discrete steps mediated by individ ual families of adhesion molecules, but rather as a series of overlapping s ynergistic interactions among adhesion molecules resulting in an adhesion c ascade. Although long thought to be mediated by distinct adhesion pathways, overlapping adhesion cascades mediate normal lymphocyte recirculation to p eripheral lymphoid tissues and inflammation-induced leukocyte migration. Th ese cascades thereby direct leukocyte migration, which is essential for the generation of effective inflammatory responses and the development of rapi d immune responses.