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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1023.)
© 2007 American Heart Association, Inc.

Vascular Biology

P-Selectin Glycoprotein Ligand-1 Is Expressed on Endothelial Cells and Mediates Monocyte Adhesion to Activated Endothelium

Paula da Costa Martins; Juan-Jesús García-Vallejo; Johannes V. van Thienen; Mar Fernandez-Borja; Janine M. van Gils; Cora Beckers; Anton J. Horrevoets; Peter L. Hordijk; Jaap-Jan Zwaginga

From the Department of Experimental Immunohematology (P.d.C.M., J.v.G., J.-J.Z.), Sanquin Research; the Department of Molecular Cell Biology and Immunology (J.-J.G.-V., M.F.-B., P.L.H.), VU Medical Center; the Department of Medical Biochemistry (J.V.v.T., A.J.H.), Academical Medical Center; the Department of Physiology (C.B.), VU Medical Center; and the Department of Immunohematology and Blood Transfusion (J.-J.Z.), Leiden University Medical Center, Leiden, The Netherlands.

Correspondence to Dr J.J. Zwaginga, Department of Immunohematology, Sanquin Research Amsterdam; Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. E-mail j.j.zwaginga{at}lumc.nl

Objective— The purpose of this study was to investigate the presence and functionality of P-selectin glycoprotein ligand-1 (PSGL-1) on activated endothelial cells (ECs).

Methods and Results— We show here that PSGL-1 is expressed at the mRNA and protein levels in umbilical vein and microvascular ECs. Furthermore, this endothelial PSGL-1 (ePSGL-1) is functional and mediates adhesion of monocytes or platelet-monocyte complexes (PMCs) to the activated endothelium in a flow model. ePSGL-1 expression was not affected by treating ECs with inflammatory stimuli (tumor necrosis factor , interleukin-1β, thrombin, or histamine). However, the functional binding capacity of ePSGL-1 to monocytes or P-selectin/Fc chimera significantly increased by stimulation of the ECs with TNF. By means of a siRNA approach to specifically knock-down the genes involved in the glycosylation of PSGL-1 we could show that tumor necrosis factor –induced glycosylation of ePSGL-1 is critical for its binding capacity.

Conclusion— Our results show that ECs express functional PSGL-1 which mediates tethering and firm adhesion of monocytes and platelets to inflamed endothelium.

We describe here the presence of PSGL-1 on human endothelial cells, both in vitro and in vivo (arteriosclerotic coronary lesions). Only activated endothelial cells showed functional PSGL-1, suggesting a role for this molecule in the arrest of monocytes during inflammation.

Key Words: P-selectin glycoprotein ligand-1 • monocyte adhesion • platelet-monocyte complexes • endothelium • glycosylation

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