What Is P-Selectin?

The initial sticky step in inflammation and immune surveillance is the rolling of leucocytes on vascular surfaces mediated by the Selectins, transmembrane, and Ca²⁺-dependent lectins. Megakaryocytes and endothelial cells express P-Selectin. It is kept in the Weibel-palate bodies of endothelial cells and the membranes of platelet granules. P-Selectin is quickly redistributed to the plasma membrane by mediating substances like thrombin, histamine, or complement.

Fig.1 Comparison of P-LE to the Structure of E-LE. P-LE is in blue and E-LE is in green. (Graves, et al., 1994)

Structure of P-Selectin

According to the publication, the human P-Selectin sequence comprises 120 amino acids with a molecular weight of around 140 kDa and a length of about 40 nm from the endothelium surface. P-Selectin usually has nine consensus repeats in a CR domain. P-Selectin associates into a homodimer by the interaction of transmembrane domains and has been suggested that the dimerization of P-Selectin and its ligand P-Selectin glycoprotein ligand 1 (PSGL-1) facilitate leukocyte rolling. A small fraction of the soluble form of P-Selectins (sP-Selectin) is derived through mRNA splicing, which lacks the exon of the transmembrane domain. P-Selectin exists in two conformations: complexed with sLex and PSGL-1 and its crystal structures contain two domains:  carbohydrate recognition domain (CRD) and Epidermal Growth Factor (EGF).

Fig.2 Comparison of the 3D structures of P-Selectin complexed with sLex (purple) representing the bend conformation and PSGL-1(blue) that represents the extended. (Tvaroška, et al., 2020)

Functions of P-Selectin in Biology

E- and P-Selectins serve as the cutaneous lymphocyte antigen and PSGL-1's binding partners (CLA). In addition, platelet-expressed P-Selectins may bind to Selectin ligands on tumor cells or to mucin fragments produced by cancer cells, establishing a connection between the platelets, the carcinoma cells, and the inflamed vasculature. P-Selectin manifests in atherosclerotic plaques in response to stimuli, because of this, atherosclerosis and coronary heart disease are influenced significantly by P-Selectin.

The term sP-Selectin refers to the soluble form of P-selectin, which is present in plasma and serum and regulates the interaction between blood cells and endothelium. It can be used as a biomarker to diagnose and forecast the need for extensive COVID-19 therapy.

Fig.3 Crizanlizumab is a monoclonal antibody that binds to P-Selectin. (Karki & Kutlar, 2021)

A humanized immunoglobulin G2 monoclonal antibody binds to and inhibits P-Selectin, preventing it from interacting with its ligand (PSGL-1). Improved microvascular flow dynamics result from blocking the interaction between endothelial cells, platelets, sickled red blood cells (RBCs), and leukocytes by the drug-binding P-Selectin on the surface of activated endothelium and platelets.

Based on the function of P-Selectin and its relationship with carbohydrates, CD BioGlyco provides Microarray Platforms including Lectin Microarray Assay to explore carbohydrates that bind to P-Selectin. We have the confidence to meet customers’ needs in this field, if you are interested in our services, please contact us for more information.

References

1. Graves, B.J.; et al. Insight into E-Selectin/ligand interaction from the crystal structure and mutagenesis of the LEC/EGF domains. Nature. 1994, 367(6463): 532–538.
2. Karki, N.R.; and Kutlar, A. P-Selectin blockade in the treatment of painful vaso-occlusive crises in sickle cell disease: A spotlight on crizanlizumab. Journal of Pain Research. 2021, Volume 14: 849–856.
3. Tvaroška, I.; et al. Selectins—the two Dr. Jekyll and Mr. Hyde faces of adhesion molecules—a review. Molecules. 2020, 25(12): 2835.