Reduced retention of radioprotective hematopoietic cells within the bone marrow microenvironmemt in CXCR4-/- chimeric mice
Reduced retention of radioprotective hematopoietic cells within the bone marrow microenvironmemt in CXCR4-/- chimeric mice
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DOI：
10.1182/blood-2005-02-0581
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发表时间：
2006-03-15
期刊：
影响因子：
20.3
通讯作者：
Louache, F
中科院分区：
文献类型：
--
作者：
Foudi, A;Jarrier, P;Louache, F
CXCR 4对造血干/祖细胞（HSPC）的生理作用尚未完全了解。在这里，我们表明，辐射保护致死照射小鼠胚胎第14.5天（E14.5）CXCR 4（-/-）胎肝（FL）细胞显着受损时，与CXCR 4（+/+）的对应物相比，但这种缺陷时，宿主移植高细胞数获救。这种数量缺陷与E14.5 CXCR 4（-/-）和CXCR 4（+/+）肝脏中造血集落形成细胞（CFC）、脾集落形成单位（CFU-S）和Lin（-）Sca-1（+）c-kit（+）细胞中类似的含量形成对比。此外，骨髓中HSPC的归巢没有改变，如CFSE染色测定所检测到的。相比之下，在用CXCR 4（-/-）FL细胞稳定重建的小鼠的循环中观察到CFC增加30倍，并且在造血达到稳态水平之前已经观察到这种增加。总之，这些数据强烈表明，受损的保留，至少在短期造血重建，导致辐射防护所需的可用祖细胞的数量减少。
The physiologic role of CXCR4 on hematopoietic stem/progenitor cells (HSPCs) is not fully understood. Here, we show that radioprotection of lethally irradiated mice by embryonic day 14.5 (E14.5) CXCR4(-/-) fetal liver (FL) cells was markedly impaired when compared with CXCR4(+/+) counterparts, but this defect was rescued when hosts were engrafted with high cell numbers. This quantitative defect contrasted with a similar content in hematopoietic colony-forming cells (CFCs), splenic colony-forming units (CFUs-S), and Lin(-) Sca-1(+) c-kit(+) cells in E14.5 CXCR4(-/-) and CXCR4(+/+) livers. In addition, the homing of HSPCs in the bone marrow was not altered as detected with a CFSE-staining assay. In contrast, a 30-fold increase in CFCs was seen in the circulation of mice stably reconstituted with CXCR4(-/-) FL cells and this increment was already observed before hematopoiesis had reached a steady-state level. Together, the data strongly suggest that impaired retention may, at least in short-term hematopoietic reconstitution, lead to a diminution in the number of available progenitors required for radioprotection.