Platelet selectin (P-selectin) (SELP)

Platelet selectin (P-selectin), also designated as CD62P, is a 140 kDa transmembrane glycoprotein stored in the alpha-granules of platelets and Weibel-Palade bodies of vascular endothelial cells [UniProt: Q95173]. Upon stimulation by agonists such as thrombin or histamine, P-selectin is rapidly translocated to the cell surface, where it facilitates the initial attachment and rolling of leukocytes on the vessel wall by binding to P-selectin glycoprotein ligand-1 (PSGL-1) [PubMed: 28813223]. This interaction is pivotal in the recruitment of inflammatory cells to sites of injury and the formation of platelet-leukocyte aggregates in thrombotic processes. In sickle cell disease, P-selectin expression is chronically upregulated, leading to the adhesion of sickled erythrocytes and leukocytes to the endothelium, which triggers painful vaso-occlusive crises [PubMed: 31743592]. Therapeutic agents like crizanlizumab target P-selectin to block these adhesive interactions, significantly reducing the frequency of pain crises in patients [FDA: Adakveo Label]. The cynomolgus monkey (Macaca fascicularis) ortholog is a critical model in drug development because it shares high sequence identity and functional similarity with human P-selectin, allowing for accurate assessment of cross-reactivity and pharmacodynamics during preclinical testing [PubMed: 15155836].

Other names

CD62PGMP-140PADGEMPlatelet activation dependent granule-external membrane proteinGranule membrane protein 140

Monoclonal antibodies such as crizanlizumab bind to the N-terminal lectin domain of P-selectin, which is the site responsible for binding to its primary ligand, P-selectin glycoprotein ligand-1 (PSGL-1). By sterically hindering this interaction, these drugs prevent the adhesion of leukocytes and sickled red blood cells to the vascular endothelium, thereby reducing vaso-occlusion, improving microcirculatory blood flow, and decreasing the frequency of inflammatory pain crises [PubMed: 31743592, FDA: Adakveo Label].