Structure and function of P-selectin glycoprotein ligand-1

Abstract

Directed emigration of leukocytes into inflammatory sites and lymphatic tissues is orchestrated by the regulated expression of adhesion and signaling molecules on cells within the vasculature. The selectin family of adhesion molecules that are expressed on activated endothelial cells (E-selectin and P-selectin), activated platelets (P-selectin), and peripheral blood leukocytes (L-selectin), mediate tethering and rolling of leukocytes to the vessel wall in the microcirculation. Selectins promote these interactions by binding to glycoconjugate ligands expressed on apposing cells. Selectin-mediated rolling is a prerequisite for firm adhesion and subsequent transendothelial migration of leukocytes into tissues. This review will focus on the structure and function of P-selectin glycoprotein ligand-1 (PSGL-1, CD162). PSGL-1 is a disulfide-bonded homodimeric mucin-like glycoprotein on leukocytes that interacts with P-, L-, and E-selectin. PSGL-1 mediates leukocyte-endothelial and leukocyte-platelet adhesion by binding to P-selectin expressed on activated endothelium and platelets and PSGL-1 mediates leukocyte-leukocyte adhesion by binding to L-selectin expressed on apposing leukocytes. PSGL-1 is unique in that it is the only selectin glycoprotein ligand that has been directly demonstrated to mediate cell-cell adhesion in vitro and in vivo.