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

302 Citations (Scopus)

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

Fingerprint

Blood Platelets
P-Selectin
Ligands
Selectins
Leukocytes
P-selectin ligand protein
Immunoglobulin G
Idiopathic Thrombocytopenic Purpura
Venules
Immunoelectron Microscopy
Antibodies
Hemostatics
Edetic Acid
Thrombin
Endothelium
Blood Vessels
Flow Cytometry
Membrane Proteins
Neutrophils
Western Blotting

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. / Frenette, Paul S.; Denis, Cécile V.; Weiss, Linnea; Jurk, Kerstin; Subbarao, Sangeetha; Kehrel, Beate; Hartwig, John H.; Vestweber, Dietmar; Wagner, Denisa D.

In: Journal of Experimental Medicine, Vol. 191, No. 8, 17.04.2000, p. 1413-1422.

Research output: Contribution to journalArticle

Frenette, PS, Denis, CV, Weiss, L, Jurk, K, Subbarao, S, Kehrel, B, Hartwig, JH, Vestweber, D & Wagner, DD 2000, 'P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo', Journal of Experimental Medicine, vol. 191, no. 8, pp. 1413-1422. https://doi.org/10.1084/jem.191.8.1413
Frenette, Paul S. ; Denis, Cécile V. ; Weiss, Linnea ; Jurk, Kerstin ; Subbarao, Sangeetha ; Kehrel, Beate ; Hartwig, John H. ; Vestweber, Dietmar ; Wagner, Denisa D. / P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. In: Journal of Experimental Medicine. 2000 ; Vol. 191, No. 8. pp. 1413-1422.
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AU - Jurk, Kerstin

AU - Subbarao, Sangeetha

AU - Kehrel, Beate

AU - Hartwig, John H.

AU - Vestweber, Dietmar

AU - Wagner, Denisa D.

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