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

Paul S. Frenette, Cécile V. Denis, Linnea Weiss, Kerstin Jurk, Sangeetha Subbarao, Beate Kehrel, John H. Hartwig, Dietmar Vestweber, Denisa D. Wagner

Research output: Contribution to journalArticle

318 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)1413-1422
Number of pages10
JournalJournal of Experimental Medicine
Volume191
Issue number8
DOIs
StatePublished - Apr 17 2000
Externally publishedYes

Keywords

  • Adhesion
  • Endothelium
  • Hemostasis
  • Inflammation
  • P-selectin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Frenette, P. S., Denis, C. V., Weiss, L., Jurk, K., Subbarao, S., Kehrel, B., Hartwig, J. H., Vestweber, D., & Wagner, D. D. (2000). P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. Journal of Experimental Medicine, 191(8), 1413-1422. https://doi.org/10.1084/jem.191.8.1413