Selectins as Targets in Inflammatory Diseases

Leukocyte recruitment is a multistep process and a key feature of tissue injury at sites of inflammation. Tissue accumulation of leukocytes is orchestrated by specific adhesion molecules regulating leukocyte-endothelial cell interactions, including rolling, firm adhesion and transmigration. Since the discovery and cloning of the selectin family of adhesion molecules (i.e. P-, E- and L-selectin) extensive investigative effort has been devoted to define the role of the selectins in the extravasation process of leukocytes in the microcirculation. Indeed, convincing evidence has documented that the selectins play a critical role in mediating leukocyte rolling along the endothelial cell lining. This review focuses on the mechanisms of leukocyte recruitment, especially leukocyte rolling, and the function and expression of the selectin family of adhesion molecules. Moreover, the therapeutic potential in targeting the selectins in selected inflammatory diseases, such as ischemia / reperfusion injury, artherosclerosis and endotoxemic liver injury will be described.