P-selectin – P-selectin glycoprotein ligand-1 interface (P-selectin – PSGL-1 interface)

The P-selectin – P-selectin glycoprotein ligand-1 (PSGL-1) interface is a critical protein-protein interaction that mediates the initial step of leukocyte recruitment to the vascular endothelium. P-selectin (CD62P) is a cell adhesion molecule stored in the Weibel-Palade bodies of endothelial cells and alpha-granules of platelets, which is rapidly translocated to the cell surface upon activation by inflammatory stimuli (UniProt: P16109). Its primary ligand, PSGL-1 (CD162), is a mucin-like glycoprotein constitutively expressed on the surface of most leukocytes (UniProt: Q14242). The binding of P-selectin to the N-terminal region of PSGL-1 facilitates leukocyte rolling along the vessel wall under physiological shear stress, a prerequisite for firm adhesion and subsequent extravasation (PubMed: 10601297). In pathological conditions such as sickle cell disease, this interaction promotes the formation of multicellular aggregates that lead to vascular occlusion and inflammation (PubMed: 31743593). Therapeutic targeting of this interface, most notably with the monoclonal antibody Crizanlizumab, aims to block these adhesive events to reduce the frequency of vaso-occlusive crises and improve microvascular blood flow (FDA: Adakveo).

Other names

CD62P-CD162 interactionP-selectin-PSGL-1 axisSELP-SELPLG interfaceP-selectin-PSGL-1 complex

Competitive inhibition of the protein-protein interaction between P-selectin and its primary ligand PSGL-1 to prevent leukocyte-endothelial and leukocyte-platelet adhesion (PubMed: 31743593).