Carbohydrate Ligands for the Leukocyte-Endothelium Adhesion Molecules, Selectins

Abstract

Much interest has been stimulated in carbohydrate biology as a result of selectin research. The three selectins, E-, L- and P-selectins are leukocyte-endothelium adhesion molecules (Brandley et al. 1990; Harlan et al. 1992; Bevilacqua et al. 1993). As discussed by Dr Klaus Ley (this volume), the three molecules are key players in mechanisms of innate immunity, for they have important roles at the initial stages of recruitment and emigration of leukocytes from the blood vascular compartment into sites of infection and injury. L-selectin, which is also involved in lymphocyte recirculation in and out of peripheral lymphoid tissues, is expressed constitutively on most types of leukocytes. E-selectin is expressed on activated endothelium, and P-selectin, which is in storage granules of platelets and endothelium, reaches the surface following cell activation. The selectins are long molecules that project from the cell surface. The special feature of these molecules is that they capture and mediate the rapid, but transient, attachment of leukocytes in the flowing blood stream to desired sites on the endothelium or to other leukocytes, and they tether and cause them to roll along the endothelial cell surface. This in turn allows cascades of other much tighter cell adhesive events to take place, mediated by other cell adhesion molecules, before the leukocytes can migrate through the endothelium and the underlying basement membrane. If the selectin-mediated rolling and tethering is inhibited, the subsequent steps are severely compromised. This knowledge has stimulated research into defining the ligands for the selectins in the hope of being able to design analogues that could serve as inhibitory, therapeutic substances for the treatment of disorders of inflammation.