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

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

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Title: A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
Author: Zhang, Lin; Orban, Martin; Lorenz, Michael; Barocke, Verena; Braun, Daniela Anne; 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

Note: Order does not necessarily reflect citation order of authors.

Citation: Zhang, Lin, Martin Orban, Michael Lorenz, Verena Barocke, Daniel Braun, Nicole Urtz, Christian Schulz, et al. 2012. A novel role of sphingosine 1-phosphate receptor s1pr1 in mouse thrombopoiesis. The Journal of Experimental Medicine 209(12): 2165-2181.
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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.
Published Version: doi:10.1084/jem.20121090
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501353/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11177912
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