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

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Abstract
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 α, 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 TNFα. 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 α–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.

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