The role of sphingosine 1-phosphate receptors in the trafficking of hematopoietic progenitor cells
The role of sphingosine 1-phosphate receptors in the trafficking of hematopoietic progenitor cells
复制标题
DOI：
10.1196/annals.1349.011
复制
发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Möhle, R
中科院分区：
文献类型：
--
作者：
Seitz, G;Boehmler, AM;Möhle, R
鞘氨醇I-磷酸（SIP）是一种普遍存在的细胞外脂质介质，由几种细胞类型，特别是活化的血小板释放。SIP的作用是由一个特定的G蛋白偶联鞘氨醇1-磷酸受体家族（S1 P1-S1 P5）介导的。我们证明SIP作为趋化因子作用于造血祖细胞，在体外吸引外周血CD 34（+）细胞。此外，SIP受体的持续激活增强了基质细胞衍生因子1（SDF-1）诱导的CXCR 4介导的信号转导。这些作用最有可能是由在原始和定向CD 34+造血祖细胞（HPC）中一致表达的S1 P1受体介导的。在体内，持续激活S1 P1的受体激动剂在归巢过程中导致增加植入。鉴于活化的血小板是细胞外SIP的主要来源，SDF-1介导的干细胞归巢可能发生在组织损伤部位以及骨髓。这可以解释先前观察到的原代造血干细胞对心肌梗死和其他疾病的组织修复的贡献。
Sphingosine I-phosphate (SIP) is an ubiquitously present extracellular lipid mediator that is released by several cell types, particularly by activated platelets. The effects of SIP are mediated by a specific family of G protein-coupled sphingosine 1-phosphate receptors (S1P1-S1P5). We demonstrate that SIP acts on hematopoietic progenitor cells as a chemotactic factor, attracting peripheral blood CD34(+) cells in vitro. Furthermore, constant activation of SIP receptors augments CXCR4-mediated signal transduction induced by stromal cell-derived factor 1 (SDF-1). These effects are most likely mediated by the S1P1 receptor consistently expressed in both primitive and committed CD34+ hematopoietic progenitor cells (HPCs). In vivo, sustained activation of S1P1 by a receptor agonist during the homing process resulted in increased engraftment. Given the fact that activated platelets represent a major source of extracellular SIP, SDF-1-mediated stem cell homing may occur at sites of tissue injury in addition to the bone marrow. This could explain the previously observed contribution of primary hematopoietic stem cells to tissue repair in myocardial infarction and other diseases.