P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells

Abstract P2Y12 blockade improves patient outcomes after myocardial infarction. As well as antithrombotic effects, anti-inflammatory effects may contribute to this beneficial clinical outcome. Here we aimed to identify potential anti-inflammatory effects of P2Y12 receptor blockers on monocytes and ma...

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Autores principales:	Patrick M. Siegel, Laura Sander, Alba Fricke, Johannes Stamm, Xiaowei Wang, Prerna Sharma, Nicole Bassler, Ya-Lan Ying, Christoph B. Olivier, Steffen U. Eisenhardt, Christoph Bode, Ingo Ahrens, Philipp Diehl, Karlheinz Peter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/02fdc9b5ec5545029a39ac063008c7a8
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spelling	oai:doaj.org-article:02fdc9b5ec5545029a39ac063008c7a82021-12-02T16:38:25ZP2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells10.1038/s41598-021-95710-32045-2322https://doaj.org/article/02fdc9b5ec5545029a39ac063008c7a82021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95710-3https://doaj.org/toc/2045-2322Abstract P2Y12 blockade improves patient outcomes after myocardial infarction. As well as antithrombotic effects, anti-inflammatory effects may contribute to this beneficial clinical outcome. Here we aimed to identify potential anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages. Using flow cytometry, migration assays, flow chambers and RNA microarrays, we investigated the effects of adenosine diphosphate (ADP) and P2Y12 receptor blockers on blood monocytes, THP-1 monocytes and THP-1 monocytes after differentiation to macrophages. P2Y12 -expressing platelets can form aggregates with monocytes in circulating blood. Mediated by platelets, ADP results in activation of the integrin receptor Mac-1 on blood monocytes, as detected by the conformation-specific single-chain antibody MAN-1. Via the same association with platelets, THP-1 monocyte adhesion to the endothelial intercellular adhesion molecule 1 (ICAM-1) is induced by ADP. P2Y12 receptor blockers prevent these ADP effects on monocytes. Interestingly, in contrast to THP-1 monocytes, THP-1 monocytes, after differentiation to macrophages, directly expressed the P2Y12 receptor and consequently ADP was found to be a potent chemoattractant. Again, P2Y12 receptor blockers antagonised this effect. Accordingly, stimulation of THP-1 macrophages with ADP caused a substantial change in gene expression pattern and upregulation of several genes associated with inflammation and atherogenesis. These data establish novel anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages, which are expected to contribute to cardiovascular risk reduction.Patrick M. SiegelLaura SanderAlba FrickeJohannes StammXiaowei WangPrerna SharmaNicole BasslerYa-Lan YingChristoph B. OlivierSteffen U. EisenhardtChristoph BodeIngo AhrensPhilipp DiehlKarlheinz PeterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patrick M. Siegel Laura Sander Alba Fricke Johannes Stamm Xiaowei Wang Prerna Sharma Nicole Bassler Ya-Lan Ying Christoph B. Olivier Steffen U. Eisenhardt Christoph Bode Ingo Ahrens Philipp Diehl Karlheinz Peter P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells
description	Abstract P2Y12 blockade improves patient outcomes after myocardial infarction. As well as antithrombotic effects, anti-inflammatory effects may contribute to this beneficial clinical outcome. Here we aimed to identify potential anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages. Using flow cytometry, migration assays, flow chambers and RNA microarrays, we investigated the effects of adenosine diphosphate (ADP) and P2Y12 receptor blockers on blood monocytes, THP-1 monocytes and THP-1 monocytes after differentiation to macrophages. P2Y12 -expressing platelets can form aggregates with monocytes in circulating blood. Mediated by platelets, ADP results in activation of the integrin receptor Mac-1 on blood monocytes, as detected by the conformation-specific single-chain antibody MAN-1. Via the same association with platelets, THP-1 monocyte adhesion to the endothelial intercellular adhesion molecule 1 (ICAM-1) is induced by ADP. P2Y12 receptor blockers prevent these ADP effects on monocytes. Interestingly, in contrast to THP-1 monocytes, THP-1 monocytes, after differentiation to macrophages, directly expressed the P2Y12 receptor and consequently ADP was found to be a potent chemoattractant. Again, P2Y12 receptor blockers antagonised this effect. Accordingly, stimulation of THP-1 macrophages with ADP caused a substantial change in gene expression pattern and upregulation of several genes associated with inflammation and atherogenesis. These data establish novel anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages, which are expected to contribute to cardiovascular risk reduction.
format	article
author	Patrick M. Siegel Laura Sander Alba Fricke Johannes Stamm Xiaowei Wang Prerna Sharma Nicole Bassler Ya-Lan Ying Christoph B. Olivier Steffen U. Eisenhardt Christoph Bode Ingo Ahrens Philipp Diehl Karlheinz Peter
author_facet	Patrick M. Siegel Laura Sander Alba Fricke Johannes Stamm Xiaowei Wang Prerna Sharma Nicole Bassler Ya-Lan Ying Christoph B. Olivier Steffen U. Eisenhardt Christoph Bode Ingo Ahrens Philipp Diehl Karlheinz Peter
author_sort	Patrick M. Siegel
title	P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells
title_short	P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells
title_full	P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells
title_fullStr	P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells
title_full_unstemmed	P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells
title_sort	p2y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including thp-1 cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/02fdc9b5ec5545029a39ac063008c7a8
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P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells

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