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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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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. |
format | Online Article Text |
id | pubmed-3501353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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