selectines

Selectins are a family of calcium-dependent cell adhesion molecules that mediate initial interactions between leukocytes and the vascular endothelium. The three members are L-selectin (CD62L), E-selectin (CD62E), and P-selectin (CD62P). They share a common architecture that includes an N-terminal lectin domain, an EGF-like domain, a mucin-like stalk, and a cytoplasmic tail, which together support rapid, transient binding under shear flow.

All selectins recognize specific carbohydrate ligands carried by leukocytes and endothelial cells. A key feature is binding to sialylated oligosaccharides such as sialyl-Lewis X. P-selectin uses PSGL-1 as a major ligand, while E-selectin also binds PSGL-1 and other ligands such as ESL-1 and CD44. L-selectin primarily interacts with ligands on high-endothelial venules (HEVs) known as PNAd, which include glycosylated mucin-like proteins such as GlyCAM-1 and CD34. Binding is calcium-dependent, enabling rapid switching of adhesion during inflammatory responses.

In physiological trafficking, selectins mediate tethering and rolling of leukocytes along activated endothelium, allowing chemokine signals to trigger integrin activation and firm adhesion for extravasation into tissues. L-selectin supports lymphocyte homing to lymph nodes, whereas E- and P-selectin participate in recruiting neutrophils, monocytes, and other leukocytes to sites of inflammation. P-selectin is stored in Weibel-Palade bodies of endothelial cells and alpha granules of platelets and is rapidly mobilized to the surface upon activation; E-selectin is induced on endothelium by inflammatory cytokines such as TNF-alpha and IL-1.

Clinical relevance includes contributions to inflammatory diseases and cancer metastasis. Therapeutic approaches targeting selectins or their ligands have been explored to reduce inappropriate leukocyte recruitment, though clinical success remains limited.