The Involvment of Hematopoietic-Specific PLC -β2 in Homing and Engraftment of Hematopoietic Stem/Progenitor Cells
The Involvment of Hematopoietic-Specific PLC -β2 in Homing and Engraftment of Hematopoietic Stem/Progenitor Cells
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DOI：
10.1007/s12015-016-9689-x
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发表时间：
2016-12-01
影响因子：
4.8
通讯作者：
Ratajczak, Mariusz Z.
中科院分区：
文献类型：
--
作者：
Adamiak, Mateusz;Suszynska, Malwina;Ratajczak, Mariusz Z.
造血干祖细胞（HSPCs）的迁移和骨髓（BM）归巢受几种信号通路的调节，在这里，我们提供了造血特异性磷脂酶C-β 2（PLC-β 2）参与这一过程的证据。这种酶参与细胞内钙的释放和蛋白激酶C（PKC）的活化。最近，我们报道了PLC-β 2促进HSPCs从BM动员到外周血（PB）中，并且这种作用是通过PLC-β 2参与粒细胞释放蛋白水解酶及其在膜脂筏解体中的作用介导的。在这里，我们报告说，除了PLC-β 2的作用，在释放的HSPCs从BM壁龛，PLC-β 2调节迁移的HSPCs响应趋化梯度的BM归巢因子，包括SDF-1，S1 P，C1 P和ATP。具体而言，来自PLC-β 2-KO小鼠的HSPC在移植到致死性辐照小鼠中后显示体内归巢和植入受损。HSPC迁移的这种减少可以通过PLC-β 2-KO小鼠中钙释放受损和血红素加氧酶1（HO-1）（一种负调节细胞迁移的酶）的高基线水平来解释。
Migration and bone marrow (BM) homing of hematopoietic stem progenitor cells (HSPCs) is regulated by several signaling pathways, and here we provide evidence for the involvement in this process of hematopoietic-specific phospholipase C-beta 2 (PLC-beta 2). This enzyme is involved in release of intracellular calcium and activation of protein kinase C (PKC). Recently we reported that PLC-beta 2 promotes mobilization of HSPCs from BM into peripheral blood (PB), and this effect is mediated by the involvement of PLC-beta 2 in the release of proteolytic enzymes from granulocytes and its role in disintegration of membrane lipid rafts. Here we report that, besides the role of PLC-beta 2 in the release of HSPCs from BM niches, PLC-beta 2 regulates the migration of HSPCs in response to chemotactic gradients of BM homing factors, including SDF-1, S1P, C1P, and ATP. Specifically, HSPCs from PLC-beta 2-KO mice show impaired homing and engraftment in vivo after transplantation into lethally irradiated mice. This decrease in migration of HSPCs can be explained by impaired calcium release in PLC-beta 2-KO mice and a high baseline level of heme oxygenase 1 (HO-1), an enzyme that negatively regulates cell migration.