Pselectin

P-selectin is a transmembrane adhesion molecule of the selectin family, encoded by the SELP gene. In humans, it is stored in Weibel-Palade bodies of activated endothelial cells and in alpha granules of platelets, and is rapidly translocated to the cell surface after cellular activation.

On the cell surface, P-selectin mediates initial tethering and rolling of leukocytes, including neutrophils and monocytes, by binding to its primary ligand, P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes. This interaction supports leukocyte recruitment under shear flow and promotes signaling that enhances integrin activation, enabling firm adhesion and subsequent transmigration. P-selectin can interact with additional ligands, contributing to a broader role in leukocyte trafficking during inflammatory responses.

P-selectin expression is tightly regulated and upregulated by stimuli such as thrombin, histamine, and inflammatory cytokines. In addition to membrane-bound P-selectin, a soluble form (soluble P-selectin) is produced by proteolytic shedding and is detectable in plasma; sP-selectin serves as a biomarker of platelet and endothelial activation in various conditions.

Physiological and pathological roles include participation in normal inflammatory responses and hemostasis, as well as involvement in thrombosis, atherosclerosis, and cancer metastasis through platelet–tumor cell interactions. Clinically, elevated P-selectin or soluble P-selectin levels are associated with several disease states.

Therapeutically, P-selectin inhibitors are under study, with crizanlizumab, a humanized anti-P-selectin antibody, approved to reduce vaso-occlusive crises in sickle cell disease. Ongoing research explores broader anti-inflammatory and anti-thrombotic applications and potential adverse effects related to impaired leukocyte recruitment.