Platelet-associated LIGHT (TNFSF14) mediates adhesion of platelets to human vascular endothelium

Sultan Celik; Harald Langer; Konstantinos Stellos; Andreas E. May; Vijay Shankar; Kerstin Kurz; Hugo A. Katus; Meinrad P. Gawaz; Thomas J. Dengler

doi:10.1160/TH07-02-0096

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(04): 798-805
DOI: 10.1160/TH07-02-0096

Platelets and Blood Cells

Schattauer GmbH

Platelet-associated LIGHT (TNFSF14) mediates adhesion of platelets to human vascular endothelium

Sultan Celik^*

¹Innere Medizin III, Universität Heidelberg, Heidelberg, Germany

,

Harald Langer^*

²Medizinische Klinik III, Eberhard Karls Universität Tübingen, Tübingen, Germany

,

Konstantinos Stellos

²Medizinische Klinik III, Eberhard Karls Universität Tübingen, Tübingen, Germany

,

Andreas E. May

²Medizinische Klinik III, Eberhard Karls Universität Tübingen, Tübingen, Germany

,

Vijay Shankar

¹Innere Medizin III, Universität Heidelberg, Heidelberg, Germany

,

Kerstin Kurz

¹Innere Medizin III, Universität Heidelberg, Heidelberg, Germany

,

Hugo A. Katus

¹Innere Medizin III, Universität Heidelberg, Heidelberg, Germany

,

Meinrad P. Gawaz^§

²Medizinische Klinik III, Eberhard Karls Universität Tübingen, Tübingen, Germany

,

Thomas J. Dengler^§

¹Innere Medizin III, Universität Heidelberg, Heidelberg, Germany

› Author Affiliations

Abstract

Summary

LIGHT (TNFSF 14) belongs to the tumor necrosis factor super-family and is expressed by different types of immune cells. Recently, LIGHT was found to be associated with platelets and released upon activation. Activation of endothelial cells by recombinant LIGHT results in pro-inflammatory and pro-thrombotic changes, qualitatively comparable to effects of CD40 ligand. Given the important role of platelet-associated CD40 ligand in vascular inflammatory responses we investigated the role of LIGHT for activation of endothelium and adhesion of platelets to endothelial cells. Expression of LIGHT was detected on thrombocytes upon exposure to ADP or TRAP-1. The expression of the LIGHT receptors TR2 and LTβR on native human endothelial cells was confirmed by FACS analysis. LIGHT mediated adhesion of platelets to endothelium significantly, occurring both under static and dynamic flow conditions. This interaction was inhibited by a monoclonal antibody to LIGHT but not a control IgG. Moreover, in-vitro stimulation of endothelial cells with recombinant soluble human LIGHT (rhLIGHT) resulted in significantly increased transcriptional and translational upregulation of inflammatory markers ICAM-1, tissue factor (TF) and IL-8. This activation of endothelial cells by LIGHT was mediated by NFκB activation and qualitatively comparable to that induced by membrane-bound CD40-ligand on transfected cells. Furthermore, plasma levels of patients with myocardial infarction, in those with ST-elevation myocardial infarction (STEMI), showed increased plasma levels of LIGHT compared with healthy controls. In conclusion, platelet-associated LIGHT is involved in adhesion of platelets to endothelium while soluble LIGHT induces a pro-inflammatory state in vascular endothelial cells. LIGHT may thus be implicated in the pathogenesis of atherosclerosis and acute coronary syndrome, as evidenced by serum levels.

Keywords

Platelet adhesion - endothelial cells - inflammation

Full Text

References

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