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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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Main Authors: Möller, Kerstin (Author) , Adolph, Oliver (Author) , Grünow, Jennifer (Author) , Elrod, Julia (Author) , Popa, Mirunda (Author) , Ghosh, Subhajit (Author) , Schwarz, Manuel (Author) , Schwale, Chrysovalandis (Author) , Grässle, Sandra (Author) , Huck, Volker (Author) , Bruehl, Claus (Author) , Wieland, Thomas (Author) , Schneider, Stefan W. (Author) , Nobiling, Rainer (Author) , Wagner, Andreas H. (Author) , Hecker, Markus (Author)
Format: Article (Journal)
Language:English
Published: 2015
In: Thrombosis and haemostasis
Year: 2015, Volume: 113, Issue: 5, Pages: 1095-1108
ISSN:2567-689X
DOI:10.1160/TH14-04-0336
Online Access: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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Author Notes: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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Summary: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.
Item Description:Gesehen am 11.12.2017
Physical Description:Online Resource
ISSN:2567-689X
DOI:10.1160/TH14-04-0336

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