Mechanism and functional impact of CD40 ligand-induced von Willebrand factor release from endothelial cells
Co-stimulation via CD154 binding to CD40, pivotal for both innate and adaptive immunity, may also link haemostasis to vascular remodelling. Here we demonstrate that human platelet-bound or recombinant soluble CD154 (sCD154) elicit the release from and tethering of ultra-large (UL) von Willebrand fac...
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| Hauptverfasser: | , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2015
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| In: |
Thrombosis and haemostasis
Year: 2015, Jahrgang: 113, Heft: 5, Pages: 1095-1108 |
| ISSN: | 2567-689X |
| DOI: | 10.1160/TH14-04-0336 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1160/TH14-04-0336 Verlag, Volltext: https://th-schattauer-de.ezproxy.medma.uni-heidelberg.de/contents/archive/issue/2210/manuscript/23911.html 
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| Verfasserangaben: | K. Möller, O. Adolph, J. Grünow, J. Elrod, M. Popa, S. Ghosh, M. Schwarz, C. Schwale, S. Grässle, V. Huck, C. Bruehl, T. Wieland, S.W. Schneider, R. Nobiling, A.H. Wagner, M. Hecker |
MARC
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| 245 | 1 | 0 | |a Mechanism and functional impact of CD40 ligand-induced von Willebrand factor release from endothelial cells |c K. Möller, O. Adolph, J. Grünow, J. Elrod, M. Popa, S. Ghosh, M. Schwarz, C. Schwale, S. Grässle, V. Huck, C. Bruehl, T. Wieland, S.W. Schneider, R. Nobiling, A.H. Wagner, M. Hecker |
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| 520 | |a Co-stimulation via CD154 binding to CD40, pivotal for both innate and adaptive immunity, may also link haemostasis to vascular remodelling. Here we demonstrate that human platelet-bound or recombinant soluble CD154 (sCD154) elicit the release from and tethering of ultra-large (UL) von Willebrand factor (vWF) multimers to the surface of human cultured endothelial cells (ECs) exposed to shear stress. This CD40-mediated ULVWF multimer release from the Weibel-Palade bodies was triggered by consecutive activation of TRAF6, the tyrosine kinase c-Src and phospholipase Cγ1 followed by inositol-1,4,5 trisphosphate-mediated calcium mobilisation. Subsequent exposure to human washed platelets caused ULVWF multimer-platelet string formation on the EC surface in a shear stress-dependent manner. Platelets tethered to these ULVWF multimers exhibited P-selectin on their surface and captured labelled monocytes from the superfusate. When exposed to shear stress and sCD154, native ECs from wild-type but not CD40 or vWF-deficient mice revealed a comparable release of ULVWF multimers to which murine washed platelets rapidly adhered, turning P-selectin-positive and subsequently capturing monocytes from the perfusate. This novel CD154-provoked ULVWF multimer-platelet string formation at normal to fast flow may contribute to vascular remodelling processes requiring the perivascular or intravascular accumulation of pro-inflammatory macrophages such as arteriogenesis or atherosclerosis. | ||
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