Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium

Abstract Double-stranded DNA (dsDNA) constitutes a potent activator of innate immunity, given its ability to bind intracellular pattern recognition receptors during viral infections or sterile tissue damage. While effects of dsDNA in immune cells have been extensively studied, dsDNA signalling and i...

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Autores principales:	Erik Gaitzsch, Thomas Czermak, Andrea Ribeiro, Yvonn Heun, Monica Bohmer, Monika Merkle, Hanna Mannell, Christian Schulz, Markus Wörnle, Joachim Pircher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3223fb986f184a3bb004e31aaba168a0
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spelling	oai:doaj.org-article:3223fb986f184a3bb004e31aaba168a02021-12-02T12:32:37ZDouble-stranded DNA induces a prothrombotic phenotype in the vascular endothelium10.1038/s41598-017-01148-x2045-2322https://doaj.org/article/3223fb986f184a3bb004e31aaba168a02017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01148-xhttps://doaj.org/toc/2045-2322Abstract Double-stranded DNA (dsDNA) constitutes a potent activator of innate immunity, given its ability to bind intracellular pattern recognition receptors during viral infections or sterile tissue damage. While effects of dsDNA in immune cells have been extensively studied, dsDNA signalling and its pathophysiological implications in non-immune cells, such as the vascular endothelium, remain poorly understood. The aim of this study was to characterize prothrombotic effects of dsDNA in vascular endothelial cells. Transfection of cultured human endothelial cells with the synthetic dsDNA poly(dA:dT) induced upregulation of the prothrombotic molecules tissue factor and PAI-1, resulting in accelerated blood clotting in vitro, which was partly dependent on RIG-I signalling. Prothrombotic effects were also observed upon transfection of endothelial cells with hepatitis B virus DNA-containing immunoprecipitates as well human genomic DNA. In addition, dsDNA led to surface expression of von Willebrand factor resulting in increased platelet-endothelium-interactions under flow. Eventually, intrascrotal injection of dsDNA resulted in accelerated thrombus formation upon light/dye-induced endothelial injury in mouse cremaster arterioles and venules in vivo. In conclusion, we show that viral or endogenous dsDNA induces a prothrombotic phenotype in the vascular endothelium. These findings represent a novel link between pathogen- and danger-associated patterns within innate immunity and thrombosis.Erik GaitzschThomas CzermakAndrea RibeiroYvonn HeunMonica BohmerMonika MerkleHanna MannellChristian SchulzMarkus WörnleJoachim PircherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Erik Gaitzsch Thomas Czermak Andrea Ribeiro Yvonn Heun Monica Bohmer Monika Merkle Hanna Mannell Christian Schulz Markus Wörnle Joachim Pircher Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium
description	Abstract Double-stranded DNA (dsDNA) constitutes a potent activator of innate immunity, given its ability to bind intracellular pattern recognition receptors during viral infections or sterile tissue damage. While effects of dsDNA in immune cells have been extensively studied, dsDNA signalling and its pathophysiological implications in non-immune cells, such as the vascular endothelium, remain poorly understood. The aim of this study was to characterize prothrombotic effects of dsDNA in vascular endothelial cells. Transfection of cultured human endothelial cells with the synthetic dsDNA poly(dA:dT) induced upregulation of the prothrombotic molecules tissue factor and PAI-1, resulting in accelerated blood clotting in vitro, which was partly dependent on RIG-I signalling. Prothrombotic effects were also observed upon transfection of endothelial cells with hepatitis B virus DNA-containing immunoprecipitates as well human genomic DNA. In addition, dsDNA led to surface expression of von Willebrand factor resulting in increased platelet-endothelium-interactions under flow. Eventually, intrascrotal injection of dsDNA resulted in accelerated thrombus formation upon light/dye-induced endothelial injury in mouse cremaster arterioles and venules in vivo. In conclusion, we show that viral or endogenous dsDNA induces a prothrombotic phenotype in the vascular endothelium. These findings represent a novel link between pathogen- and danger-associated patterns within innate immunity and thrombosis.
format	article
author	Erik Gaitzsch Thomas Czermak Andrea Ribeiro Yvonn Heun Monica Bohmer Monika Merkle Hanna Mannell Christian Schulz Markus Wörnle Joachim Pircher
author_facet	Erik Gaitzsch Thomas Czermak Andrea Ribeiro Yvonn Heun Monica Bohmer Monika Merkle Hanna Mannell Christian Schulz Markus Wörnle Joachim Pircher
author_sort	Erik Gaitzsch
title	Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium
title_short	Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium
title_full	Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium
title_fullStr	Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium
title_full_unstemmed	Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium
title_sort	double-stranded dna induces a prothrombotic phenotype in the vascular endothelium
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3223fb986f184a3bb004e31aaba168a0
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Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium

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