Selectin-sialoside interaction (Selectins)

Selectins (E-, L-, and P-selectin) are a family of cell surface glycoproteins that function as calcium-dependent (C-type) lectins, mediating the initial tethering and rolling of leukocytes on the vascular endothelium [1, 3, 4]. This process is essential for the recruitment of immune cells to sites of inflammation and injury. Selectins achieve this by binding to specific sialylated and fucosylated carbohydrate ligands, most notably the tetrasaccharide Sialyl Lewis X (sLeX), which is presented on scaffold proteins like P-selectin glycoprotein ligand-1 (PSGL-1) [1, 6, 12]. E-selectin is primarily expressed on activated endothelial cells, P-selectin on activated platelets and endothelial cells, and L-selectin on most circulating leukocytes [3, 5, 8]. Dysregulation of these interactions plays a critical role in the pathogenesis of various diseases, including vaso-occlusive crises in sickle cell disease, where P-selectin mediates the adhesion of sickled red blood cells and leukocytes to the vessel wall [2, 13, 16]. Furthermore, selectin-sialoside interactions are involved in chronic inflammatory disorders and the hematogenous metastasis of cancer cells, which exploit these adhesion mechanisms to extravasate into distant tissues [3, 6, 11]. Therapeutic targeting of this axis has led to the development of monoclonal antibodies like crizanlizumab and glycomimetics like uproleselan, which aim to block these adhesive interactions to alleviate symptoms and prevent disease progression [1, 12, 20].

Other names

CD62ECD62LCD62PSelectin familyE-selectinL-selectinP-selectinSialyl Lewis X-selectin interactionLECAM-1ELAM-1GMP-140PADGEMLAM-1Mel-14

Inhibition of selectin-mediated cell adhesion by blocking the interaction between selectins and their sialylated carbohydrate ligands.