P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo

The platelet plays a pivotal role in maintaining vascular integrity. In a m anner similar to leukocytes, platelets interact with selectins expressed on activated endothelium. P-selectin glycoprotein ligand 1 (PSGL-1) is the ma in P-selectin ligand expressed on leukocytes. Searching for platelet ligand (s), we used a P-selectin-immunoglobulin G (IgG) chimera to affinity purify sur face-biotinylated proteins from platelet lysates. P-selectin-bound lig ands were eluted with ethylenediaminetetraacetic acid. An similar to 210-kD biotinylated protein was isolated from both human neutrophil and platelet preparations. A band of the same size was also immunopurified from human pl atelets using a monoclonal anti-human PSGL-1 antibody and could be blotted with P-selectin-IgG. Under reducing conditions, both the predicted PSGL-1 s imilar to 210-kD dimer and the similar to 120-kD monomer were isolated from platelets. Comparative immunoelectron microscopy and Western blotting expe riments suggested that platelet PSGL-1 expression is 25-100-fold lower than that of leukocytes. However, patients with chronic idiopathic thrombocytop enic purpura who harbor predominantly young platelets displayed greater exp ression, indicating that PSGL-1 expression may be decreased during platelet aging. By flow cytometry, thrombin-activated platelets from normal individ uals exhibited greater expression than those unstimulated. An inhibitory an ti-PSGL-1 antibody significantly reduced platelet rolling in mesenteric ven ules, as observed by intravital microscopy. Our results indicate that funct ional PSGL-1 is expressed on platelets, and suggest an additional mechanism by which selectins and their ligands participate in inflammatory and/or he mostatic responses.