P-selectin glycoprotein ligand-1 is expressed on endothelial cells and mediates monocyte adhesion to activated endothelium.
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).


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 alpha, interleukin-1beta, 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 TNFalpha. 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 alpha-induced glycosylation of ePSGL-1 is critical for its binding capacity.


CONCLUSIONS
Our results show that ECs express functional PSGL-1 which mediates tethering and firm adhesion of monocytes and platelets to inflamed endothelium.
da Costa Martins
Paula
P
Department of Experimental Immunohematology, Sanquin Research, Leiden, The Netherlands.
García-Vallejo
Juan-Jesús
JJ
van Thienen
Johannes V
JV
Fernandez-Borja
Mar
M
van Gils
Janine M
JM
Beckers
Cora
C
Horrevoets
Anton J
AJ
Hordijk
Peter L
PL
Zwaginga
Jaap-Jan
JJ
D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D018613:Microscopy, Confocal; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D012313:RNA