ABSTRACT
Circulating leukocytes cross an endothelium in a multi-step, reversible process that involves sequential interaction of selectins, integrins, and chemokines. In the first step, interactions between selectins on the surface of the endothelium with carbohydrate counter receptors on leukocytes initiate a ‘‘tethering’’ of cells along the endothelium within the shear forces of the bloodstream, resulting in dramatic slowing and rolling along the endothelium. Integrins, located on the surface of leukocytes, are next very rapidly activated by chemokines, a process that requires signaling through Gai-linked receptors. The activation of integrins allows for the firm arrest of leukocytes through interactions with cell adhesion molecules (CAMs) on the endothelium. Once arrested, leukocytes can penetrate the endothelial lining and travel into tissue via diapadesis. During this process leukocytes are directed by chemoattractant gradients to migrate across the endothelium and through the basal lamina and extracellular matrix into tissue (1).
