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A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis

Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mu...

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Autores principales: Zhang, Lin, Orban, Martin, Lorenz, Michael, Barocke, Verena, Braun, Daniel, Urtz, Nicole, Schulz, Christian, von Brühl, Marie-Luise, Tirniceriu, Anca, Gaertner, Florian, Proia, Richard L., Graf, Thomas, Bolz, Steffen-Sebastian, Montanez, Eloi, Prinz, Marco, Müller, Alexandra, von Baumgarten, Louisa, Billich, Andreas, Sixt, Michael, Fässler, Reinhard, von Andrian, Ulrich H., Junt, Tobias, Massberg, Steffen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501353/
https://www.ncbi.nlm.nih.gov/pubmed/23148237
http://dx.doi.org/10.1084/jem.20121090
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author Zhang, Lin
Orban, Martin
Lorenz, Michael
Barocke, Verena
Braun, Daniel
Urtz, Nicole
Schulz, Christian
von Brühl, Marie-Luise
Tirniceriu, Anca
Gaertner, Florian
Proia, Richard L.
Graf, Thomas
Bolz, Steffen-Sebastian
Montanez, Eloi
Prinz, Marco
Müller, Alexandra
von Baumgarten, Louisa
Billich, Andreas
Sixt, Michael
Fässler, Reinhard
von Andrian, Ulrich H.
Junt, Tobias
Massberg, Steffen
author_facet Zhang, Lin
Orban, Martin
Lorenz, Michael
Barocke, Verena
Braun, Daniel
Urtz, Nicole
Schulz, Christian
von Brühl, Marie-Luise
Tirniceriu, Anca
Gaertner, Florian
Proia, Richard L.
Graf, Thomas
Bolz, Steffen-Sebastian
Montanez, Eloi
Prinz, Marco
Müller, Alexandra
von Baumgarten, Louisa
Billich, Andreas
Sixt, Michael
Fässler, Reinhard
von Andrian, Ulrich H.
Junt, Tobias
Massberg, Steffen
author_sort Zhang, Lin
collection PubMed
description Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P–S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia.
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spelling pubmed-35013532013-05-19 A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis Zhang, Lin Orban, Martin Lorenz, Michael Barocke, Verena Braun, Daniel Urtz, Nicole Schulz, Christian von Brühl, Marie-Luise Tirniceriu, Anca Gaertner, Florian Proia, Richard L. Graf, Thomas Bolz, Steffen-Sebastian Montanez, Eloi Prinz, Marco Müller, Alexandra von Baumgarten, Louisa Billich, Andreas Sixt, Michael Fässler, Reinhard von Andrian, Ulrich H. Junt, Tobias Massberg, Steffen J Exp Med Article Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P–S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia. The Rockefeller University Press 2012-11-19 /pmc/articles/PMC3501353/ /pubmed/23148237 http://dx.doi.org/10.1084/jem.20121090 Text en © 2012 Zhang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Zhang, Lin
Orban, Martin
Lorenz, Michael
Barocke, Verena
Braun, Daniel
Urtz, Nicole
Schulz, Christian
von Brühl, Marie-Luise
Tirniceriu, Anca
Gaertner, Florian
Proia, Richard L.
Graf, Thomas
Bolz, Steffen-Sebastian
Montanez, Eloi
Prinz, Marco
Müller, Alexandra
von Baumgarten, Louisa
Billich, Andreas
Sixt, Michael
Fässler, Reinhard
von Andrian, Ulrich H.
Junt, Tobias
Massberg, Steffen
A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
title A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
title_full A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
title_fullStr A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
title_full_unstemmed A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
title_short A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
title_sort novel role of sphingosine 1-phosphate receptor s1pr1 in mouse thrombopoiesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501353/
https://www.ncbi.nlm.nih.gov/pubmed/23148237
http://dx.doi.org/10.1084/jem.20121090
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