G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4
G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4
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DOI：
10.1038/ni813
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发表时间：
2002-07-01
影响因子：
30.5
通讯作者：
Lapidot, T
中科院分区：
文献类型：
--
作者：
Petit, I;Szyper-Kravitz, M;Lapidot, T
粒细胞集落刺激因子（G-CSF）诱导的造血干细胞动员广泛应用于临床移植，但其机制尚不清楚。我们在这里报告，G-CSF诱导减少趋化因子基质细胞衍生因子1（SDF-1）和增加其受体CXCR 4在骨髓（BM），而它们的蛋白质表达在血液中的影响较小。BM SDF-1的逐渐减少主要是由于其被中性粒细胞弹性蛋白酶降解，与干细胞动员相关。弹性蛋白酶抑制剂降低了这两种活性。中和CXCR 4或SDF-1抗体可抑制人和鼠干细胞动员，证明细胞流出中的SDF-1-CXCR 4信号传导。我们认为，SDF-1-CXCR 4相互作用的操纵可能是一种手段，控制BM和血液之间的祖细胞导航，以改善临床干细胞移植的结果。
Granulocyte colony-stimulating factor (G-CSF)-induced hematopoietic stem cell mobilization is widely used for clinical transplantation; however, the mechanism is poorly understood. We report here that G-CSF induced a reduction of the chemokine stromal cell-derived factor 1 (SDF-1) and an increase in its receptor CXCR4 in the bone marrow (BM), whereas their protein expression in the blood was less affected. The gradual decrease of BM SDF-1, due mostly to its degradation by neutrophil elastase, correlated with stem cell mobilization. Elastase inhibition reduced both activities. Human and murine stem cell mobilization was inhibited by neutralizing CXCR4 or SDF-1 antibodies, demonstrating SDF-1-CXCR4 signaling in cell egress. We suggest that manipulation of SDF-1-CXCR4 interactions may be a means with which to control the navigation of progenitors between the BM and blood to improve the outcome of clinical stem cell transplantation.