Journal articles
TRAIL/Apo2L Mediates the Release of Procoagulant Endothelial Microparticles Induced by Thrombin In Vitro A Potential Mechanism Linking Inflammation and Coagulation
Abstract : 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-␣ 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 B. Moreover, sTRAIL modulated intercellular adhesion molecule-1 and interleukin-8 expression induced by thrombin by a downstream pathway involving nuclear factor B 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. (Circ Res. 2009;104:943-951.)
Cited literature [50 references]
https://hal-amu.archives-ouvertes.fr/hal-02478114
Contributor : Administrateur Hal Amu <>
Submitted on : Thursday, February 13, 2020 - 5:14:11 PM
Last modification on : Wednesday, August 19, 2020 - 12:08:23 PM
Long-term archiving on: : Thursday, May 14, 2020 - 5:09:42 PM
Contributor : Administrateur Hal Amu <>
Submitted on : Thursday, February 13, 2020 - 5:14:11 PM
Last modification on : Wednesday, August 19, 2020 - 12:08:23 PM
Long-term archiving on: : Thursday, May 14, 2020 - 5:09:42 PM
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