S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release
| Autor: | Orit Kollet, Shiri Cohen-Gur, Shoham Shivtiel, Andrew J. Morris, Alexander Kalinkovich, Amir Schajnovitz, Tsvee Lapidot, Kfir Lapid, Mariusz Z. Ratajczak, Aya Ludin, Chihwa Kim, Yossi Ovadya, Tomer Itkin, Yaron Vagima, Karin Golan |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Benzylamines Stromal cell Hematopoiesis and Stem Cells Immunology Fluorescent Antibody Technique Biology Cyclams Biochemistry Colony-Forming Units Assay Mice Bone Marrow Cell Movement Heterocyclic Compounds Sphingosine Granulocyte Colony-Stimulating Factor medicine Animals Progenitor cell Hematopoietic Stem Cell Mobilization Cells Cultured Mice Knockout Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology Hematology Flow Cytometry Hematopoietic Stem Cells Chemokine CXCL12 Cell biology Endothelial stem cell Mice Inbred C57BL Haematopoiesis Phosphotransferases (Alcohol Group Acceptor) Receptors Lysosphingolipid medicine.anatomical_structure Female Bone marrow Stem cell Lysophospholipids Stromal Cells Reactive Oxygen Species Signal Transduction |
| Zdroj: | Blood. 119(11) |
| ISSN: | 1528-0020 |
| Popis: | The mechanisms of hematopoietic progenitor cell egress and clinical mobilization are not fully understood. Herein, we report that in vivo desensitization of Sphingosine-1-phosphate (S1P) receptors by FTY720 as well as disruption of S1P gradient toward the blood, reduced steady state egress of immature progenitors and primitive Sca-1+/c-Kit+/Lin− (SKL) cells via inhibition of SDF-1 release. Administration of AMD3100 or G-CSF to mice with deficiencies in either S1P production or its receptor S1P1, or pretreated with FTY720, also resulted in reduced stem and progenitor cell mobilization. Mice injected with AMD3100 or G-CSF demonstrated transient increased S1P levels in the blood mediated via mTOR signaling, as well as an elevated rate of immature c-Kit+/Lin− cells expressing surface S1P1 in the bone marrow (BM). Importantly, we found that S1P induced SDF-1 secretion from BM stromal cells including Nestin+ mesenchymal stem cells via reactive oxygen species (ROS) signaling. Moreover, elevated ROS production by hematopoietic progenitor cells is also regulated by S1P. Our findings reveal that the S1P/S1P1 axis regulates progenitor cell egress and mobilization via activation of ROS signaling on both hematopoietic progenitors and BM stromal cells, and SDF-1 release. The dynamic cross-talk between S1P and SDF-1 integrates BM stromal cells and hematopoeitic progenitor cell motility. |
| Databáze: | OpenAIRE |
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