A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
12.11.2012
Zhang L, Orban M, Lorenz M, Barocke V, Braun D, Urtz N, Schulz C, von Brühl ML, Tirniceriu A, Gaertner F, Proia RL, Graf T, Bolz SS, Montanez E, Prinz M, Müller A, von Baumgarten L, Billich A, Sixt M, Fässler R, von Andrian UH, Junt T, Massberg S.
J Exp Med. 2012;209(12):2165-81.
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. 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.
