TRAIL/Apo2L mediates the release of procoagulant endothelial microparticles induced by thrombin in vitro: a potential mechanism linking inflammation and coagulation.
[en] Microparticles are small vesicles playing a crucial role in cell communication by promoting prothrombotic and proinflammatory responses. However, the molecular mechanisms underlying their release are still elusive. We previously established that thrombin promoted the generation of endothelial microparticles (EMPs). In the present study, gene profiling identified TRAIL/Apo2L, a cytokine belonging to the tumor necrosis factor-alpha superfamily, as a target of thrombin. Thrombin increased the expression of cell-associated and soluble forms of TRAIL (sTRAIL) in HMEC-1 cells and human umbilical vein endothelial cells (HUVECs). Blocking TRAIL by specific antibodies or by small interfering RNA reduced both the number and the procoagulant activity of EMPs released by thrombin. Consistent with an involvement of sTRAIL in thrombin-induced EMP release, we showed that (1) exogenously added sTRAIL generated procoagulant EMPs; (2) supernatants from thrombin-stimulated endothelial cells induced EMP release by HMEC-1 cells and HUVECs, whereas those recovered from TRAIL knockdown endothelial cells displayed no effect. TRAIL/TRAIL-R2 complex mediated EMP release by initiating the recruitment of adaptor proteins and the activation of nuclear factor kappaB. Moreover, sTRAIL modulated intercellular adhesion molecule-1 and interleukin-8 expression induced by thrombin by a downstream pathway involving nuclear factor kappaB activation. Our data reveal a novel mechanism controlling EMP release and identify TRAIL as a key partner in the pathway linking coagulation and inflammation elicited by thrombin.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Simoncini, Stephanie ✱; Faculte de Pharmacie, Institut National de la Santé et de la Recherche Médicale UMR608, Physiopathologie de l'Endothelium, Universite Mediterranee, Marseille, France
Njock, Makon-Sébastien ✱; Faculte de Pharmacie, Institut National de la Santé et de la Recherche Médicale UMR608, Physiopathologie de l'Endothelium, Universite Mediterranee, Marseille, France
Robert, Stephane; Faculte de Pharmacie, Institut National de la Santé et de la Recherche Médicale UMR608, Physiopathologie de l'Endothelium, Universite Mediterranee, Marseille, France
Camoin-Jau, Laurence; Faculte de Pharmacie, Institut National de la Santé et de la Recherche Médicale UMR608, Physiopathologie de l'Endothelium, Universite Mediterranee, Marseille, France
Sampol, Jose; Faculte de Pharmacie, Institut National de la Santé et de la Recherche Médicale UMR608, Physiopathologie de l'Endothelium, Universite Mediterranee, Marseille, France
Harle, Jean-Robert; Faculte de Pharmacie, Institut National de la Santé et de la Recherche Médicale UMR608, Physiopathologie de l'Endothelium, Universite Mediterranee, Marseille, France
Nguyen, Catherine; Institut National de la Sante et de la Recherche Medicale U928 (C.N.), Technologies Avancees pour le Genome et la Clinique, Marseille, France
Dignat-George, Francoise; Faculte de Pharmacie, Institut National de la Santé et de la Recherche Médicale UMR608, Physiopathologie de l'Endothelium, Universite Mediterranee, Marseille, France
Anfosso, Francine; Faculte de Pharmacie, Institut National de la Santé et de la Recherche Médicale UMR608, Physiopathologie de l'Endothelium, Universite Mediterranee, Marseille, France
✱ These authors have contributed equally to this work.
Language :
English
Title :
TRAIL/Apo2L mediates the release of procoagulant endothelial microparticles induced by thrombin in vitro: a potential mechanism linking inflammation and coagulation.
Publication date :
23 April 2009
Journal title :
Circulation Research
ISSN :
0009-7330
eISSN :
1524-4571
Publisher :
Lippincott Williams & Wilkins, United States - Maryland
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