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

Zhang, L., Orban, M., Lorenz, M., Barocke, V., Braun, D., Urtz, N., et al. (2012). A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis. JOURNAL OF EXPERIMENTAL MEDICINE, 209(12), 2165-2181. doi:10.1084/jem.20121090.

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 Creators:
Zhang, Lin1, Author
Orban, Martin1, Author
Lorenz, Michael2, 3, 4, Author              
Barocke, Verena1, Author
Braun, Daniel1, Author
Urtz, Nicole1, Author
Schulz, Christian1, Author
von Bruehl, Marie-Luise1, Author
Tirniceriu, Anca1, Author
Gaertner, Florian1, Author
Proia, Richard L.1, Author
Graf, Thomas1, Author
Bolz, Steffen-Sebastian1, Author
Montanez, Eloi5, Author              
Prinz, Marco1, Author
Mueller, Alexandra1, Author
von Baumgarten, Louisa1, Author
Billich, Andreas1, Author
Sixt, Michael5, Author              
Fässler, Reinhard5, Author              
von Andrian, Ulrich H.1, AuthorJunt, Tobias1, AuthorMassberg, Steffen1, Author more..
Affiliations:
1external, ou_persistent22              
2Max Planck Institute for Medical Research, ou_1125545              
3Emeritus Group Biophysics, ou_1497712              
4Department of Biomedical Optics, ou_1497699              
5Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: DEMARCATION MEMBRANE SYSTEM; PROTEIN-COUPLED RECEPTOR; HEMATOPOIETIC STEM-CELL; IN-VIVO; PLATELET PRODUCTION; LYMPHOCYTE EGRESS; BLOOD-PLATELETS; RETICULATED PLATELETS; HUMAN MEGAKARYOCYTES; VASCULAR MATURATION
 Abstract: 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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Language(s): eng - English
 Dates: 2012-11-19
 Publication Status: Published in print
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000311295600005
DOI: 10.1084/jem.20121090
 Degree: -

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Title: JOURNAL OF EXPERIMENTAL MEDICINE
Source Genre: Journal
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Publ. Info: 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA : ROCKEFELLER UNIV PRESS
Pages: - Volume / Issue: 209 (12) Sequence Number: - Start / End Page: 2165 - 2181 Identifier: ISSN: 0022-1007