Published online before print February 22, 2007, doi: 10.1161/ATVBAHA.107.140442
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2007 American Heart Association, Inc.
Vascular Biology |
P-Selectin Glycoprotein Ligand-1 Is Expressed on Endothelial Cells and Mediates Monocyte Adhesion to Activated Endothelium
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-1ß, 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
Related Article:
Arterioscler. Thromb. Vasc. Biol. 2007 27: 990-992.
This article has been cited by other articles:
 |
|
 |
|
  E. E. Eriksson No detectable endothelial- or leukocyte-derived L-selectin ligand activity on the endothelium in inflamed cremaster muscle venules J. Leukoc. Biol., July 1, 2008; 84(1): 93 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tjwa, L. Bellido-Martin, Y. Lin, E. Lutgens, S. Plaisance, F. Bono, N. Delesque-Touchard, C. Herve, R. Moura, A. D. Billiau, et al. Gas6 promotes inflammation by enhancing interactions between endothelial cells, platelets, and leukocytes Blood, April 15, 2008; 111(8): 4096 - 4105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vowinkel, K. C. Wood, K. Y. Stokes, J. Russell, A. Tailor, C. Anthoni, N. Senninger, C. F. Krieglstein, and D. N. Granger Mechanisms of platelet and leukocyte recruitment in experimental colitis Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G1054 - G1060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Koenen, P. von Hundelshausen, and C. Weber Inflammatory Blues Turns Velvet Skin Into Rawhide: Monocyte Rolling on Modified Endothelial PSGL-1 Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 990 - 992. [Full Text] [PDF]
|
|