Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells.
Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells.
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DOI：
10.1038/leu.2011.62
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发表时间：
2011-08
期刊：
影响因子：
11.4
通讯作者：
Lapidot, T.
中科院分区：
文献类型：
--
作者：
Dar, A.;Schajnovitz, A.;Lapid, K.;Kalinkovich, A.;Itkin, T.;Ludin, A.;Kao, W-M;Battista, M.;Tesio, M.;Kollet, O.;Cohen, N. N.;Margalit, R.;Buss, E. C.;Baleux, F.;Oishi, S.;Fujii, N.;Larochelle, A.;Dunbar, C. E.;Broxmeyer, H. E.;Frenette, P. S.;Lapidot, T.
造血祖细胞的稳态流出可以通过动员剂如AMD 3100快速放大，然而，其机制知之甚少。我们报告说，AMD 3100增加了趋化因子SDF-1向小鼠和非人灵长类动物循环的稳态释放。抗CXCR 4或SDF-1的中和抗体抑制稳态和AMD 3100诱导的SDF-1释放，并减少鼠祖细胞相对于成熟白细胞的流出。骨内注射生物素化的SDF-1也增强了这种趋化因子的释放和鼠祖细胞的动员。AMD 3100直接诱导CXCR 4+人骨髓成骨细胞和内皮细胞释放SDF-1，并以CXCR 4/JNK依赖性方式激活uPA。此外，ROS抑制减少了AMD 3100诱导的SDF-1释放、循环uPA活化和祖细胞动员。去甲肾上腺素处理（模拟急性应激）可迅速增加SDF-1释放和祖细胞动员，而β2-肾上腺素能拮抗剂可抑制稳态和AMD 3100诱导的小鼠SDF-1释放和祖细胞动员。总之，这项研究表明，SDF-1从骨髓基质细胞释放到循环中，是造血祖细胞稳态流出和快速动员所必需的关键机制，但不是成熟的白细胞。
Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine SDF-1 to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady-state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4+ human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, while β2-adrenergic antagonist inhibited both steady-state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes.
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DOI：
10.1084/jem.20092210
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allende ML;Tuymetova G;Lee BG;Bonifacino E;Wu YP;Proia RL
通讯作者：
Proia RL
DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
20.3
作者：
Christopher, Matthew J.;Liu, Fulu;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
4.3
作者：
Hess, David A.;Bonde, Jesper;Nolta, Jan A.
通讯作者：
Nolta, Jan A.
影响因子：
20.3
作者：
Hattori, K;Heissig, B;Moore, MAS
通讯作者：
Moore, MAS