摘要
目的探讨基质细胞衍生因子-1（SDF-1）及其特异性受体CXCR4在G-CSF诱导的造血干／祖细胞（HSPC）动员中的作用。方法应用酶联免疫吸附实验（ELISA）、免疫组织化学、流式细胞术等方法检测健康供者稳态及G-CSF动员过程中骨髓、外周血SDF-1／CXCR4的变化，并应用SDF-1中和性抗体阻断BALB／c小鼠SDF-1信号通路，进一步验证SDF-1／CXCR4在动员中的作用。结果G-CSF动员前骨髓和外周血的SDF-1浓度分别为（7．23±0．66）μg/L和（5．43±0．35）μg／L，动员后分别为（5．88±1．03）μg／L和（5．42±0．52）μg/L。动员后骨髓SDF-1蛋白水平下降（P＜0．05），骨髓和外周血之间的SDF-1浓度梯度消失（P＞0．05）；稳态骨髓、动员后骨髓和动员后外周血的CD34^＋ CXCR4^＋细胞在CD34^＋细胞群中的比例分别为（40．98±21．56）％、（65．80±24．68）％和（27．54±26．03）％。动员后CXCR4在骨髓CD34^＋胞上表达增加（P＜0．05），而外周血CD34^＋细胞CXCR4表达降低（P＜0．05）。SDF-1中和性抗体可降低G-CSF动员的BALB／c小鼠外周血成熟白细胞和祖细胞集落数量（P＜0．05）。结论骨髓中SDF-1水平的降低以及CXCR4在HSPC上表达的下降促进了G-CSF介导的动员的发生。
Objective To explore the role of stromal cell-derived factor （ SDF-1） and its specific receptor CXCR4 in the G-CSF-induced hematopoietic stem/progenitor ceils （HSPCs） mobilization in human healthy donor. Methods The changes of SDF-1/CXCR4 in bone marrow （BM） and peripheral blood （PB） of healthy donors during G-CSF-induced mobilization were detected by enzyme-linked immunosorbent assay （ELISA）, immunohistological staining and flow cytometry. SDF-1 neutralizing antibody wes injected into BALB/c mice to further test its effect on mobilization. Results SDF-1 concentration in mobilized BM （mBM）, steady state BM （ssBM） and PB were（7.23±0.66）μg/L , （5.43±0.35） μg/L and（5.42 ± 0.52 ） μg/L, respectively. SDF-1 protein levels were decreased in the BM （ P 〈 0. 05 ） after 5-day G-CSF injection, and its concentration gradient between BM and PB disappeared （P 〉0.05 ）. Significant up-regulation of CXCR4 expression was observed on mBM CD34 ^＋ ceils in healthy donors. The rate of CXCR4 expression on CD34^＋ cells in ssBM, mBM and mobilized PB were （40.98 ± 21.56） %, （65.80 ± 24.68） % and （27.54 ± 26.03） % , respectively. Comparing with that in ssBM and mBM, CXCR4 expression on mobilized PB CD34^＋ cells were significantly decreased （ P 〈 0.05 ）. Inhibition of SDF-1 signal by blocking monoclonal antibodies significantly reduced G-CSF-induced mobilization in BALB/c mice. This resulted in significant decrease of white blood cell count and progenitors mobilized into peripheral circulation. Conclusion G-CSF induces HSPCs mobilization by decreasing bone marrow SDF-1 and down-regulating CXCR4 expression on HSPCs.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2007年第2期98-102,共5页
Chinese Journal of Hematology
基金
天津市基础研究重点项目基金资助（043803111,033801411）.
