Selectin P (P-selectin) (SELP)

Selectin P (P-selectin) is a 140 kDa type I transmembrane glycoprotein that functions as a critical cell adhesion molecule within the vascular system (UniProt: P16109). It is primarily sequestered in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells, but is rapidly translocated to the cell surface upon activation by inflammatory stimuli such as thrombin or cytokines (NCBI: 6403). Once expressed, P-selectin mediates the initial tethering and rolling of leukocytes along the vessel wall by binding to P-selectin glycoprotein ligand-1 (PSGL-1) (PMID: 24561236). This process is essential for the recruitment of immune cells to sites of injury and inflammation, but also facilitates platelet-leukocyte aggregates that contribute to thrombotic and inflammatory cascades. In pathological conditions like sickle cell disease, the P-selectin pathway is chronically over-activated, leading to abnormal adhesion of sickled red blood cells and leukocytes to the endothelium, which results in vaso-occlusive crises and impaired microcirculatory flow (Ataga et al., NEJM 2017). Therapeutic targeting of P-selectin, most notably with the humanized monoclonal antibody crizanlizumab, effectively blocks these adhesive interactions and has been shown to significantly reduce the frequency of pain crises (FDA: Adakveo). Beyond hematology, P-selectin is implicated in the progression of atherosclerosis, deep vein thrombosis, and the metastatic spread of certain cancers, making it a versatile target for anti-inflammatory and anti-thrombotic therapies. Monitoring soluble P-selectin levels in plasma serves as a valuable biomarker for assessing endothelial dysfunction and platelet activation in clinical settings.

Other names

CD62PGMP-140PADGEMGranule membrane protein 140Platelet activation dependent granule-external membrane proteinP-selectin

P-selectin inhibitors, such as the monoclonal antibody crizanlizumab, bind to the P-selectin protein on the surface of activated endothelial cells and platelets. This binding prevents the interaction between P-selectin and its primary ligand, P-selectin glycoprotein ligand-1 (PSGL-1), which is found on leukocytes. By blocking this adhesion, these drugs inhibit leukocyte rolling and the subsequent formation of cell clusters that lead to vaso-occlusion and inflammation (PMID: 28004914).