B. Background and Significance Leukocyte trafficking into sites of infection and tissue injury is a multistep process that is regulated by the coordinated expression of adhesion and signaling molecules (1). Flowing leukocytes tether to and roll on the vessel wall, then adhere more firmly, and finally emigrate between endothelial cells into the underlying tissues. Binding of selectins to cell-surface glycoconjugates initiates tethering and rolling (2-4). Binding of leukocyte integrins to immunoglobulin (Ig)-like molecules and other ligands slows rolling velocities, promotes firm adhesion, and directs migration (5). Cytokines, thrombin, histamine, and other mediators initiate the inflammatory cascade by stimulating endothelial cells to express adhesion molecules, chemokines, and lipid autacoids (6). Rolling leukocytes, in turn, receive signals from engagement of selectins, selectin ligands, and chemokines that promote integrin-dependent adhesion, signaling, and migration. Leukocytes also use selectins and integrins to interact with activated platelets and with other leukocytes (2). These multicellular interactions at the vascular surface link the hemostatic and inflammatory responses to tissue injury. Combinatorial diversity in expression of adhesion and signaling molecules controls the number and type of leukocytes recruited to a particular site, as well as the duration of the response. Dysregulated expression of these molecules promotes excessive accumulation of leukocytes, whose effector responses contribute to acute and chronic inflammatory diseases, thrombosis, and atherosclerosis (2).
Showing the most recent 10 out of 66 publications
