GM-CSF诱导人脐血CD34^+造血干细胞上CXCR3的表达  

CXCR3 expression on CD34^+ hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

作　　者：谭锦泉[1] 黄保军[1] 王红艳[1] 王明军[1] 郭克泰[1] 秦卫兵[1] 张学军[2] Per S.Skov Lars K.Poulsen 

机构地区：[1]安徽医科大学免疫学教研室,合肥230032 [2]安徽医科大学皮肤性病学教研室,合肥230032 [3]国立哥本哈根大学变态反应研究室

出　　处：《安徽医科大学学报》2001年第1期5-11,共7页Acta Universitatis Medicinalis Anhui

基　　金：中国国家自然科学基金!(编号 3 9870 674);安徽省自然科学基金!(编号 9843 663 0 );安徽省教育厅科学研究基金! (编号 98JL0 63 )

摘　　要：目的　研究GM CSF诱导人脐血CD34 + 造血干细胞上CXCR3的表达。方法　采用流式细胞仪 ,实时定量逆转录PCR(RT PCR)分析 ,及其配体γIP 10和Mig诱导的趋化和粘附作用分析。结果　CXCR3也表达在受GM CSF刺激后的CD34 + 造血干细胞上 ,但它在新鲜分离的CD34 + 造血干细胞上不表达。应用实时定量逆转录PCR技术检测新鲜分离的CD34 + 造血干细胞有较低水平的CXCR3mRNA表达 ,而GM CSF能上调CXCR3的表达。用抗CXCR3单克隆抗体 (mAb)能阻断γIP 10和Mig诱导的造血干细胞趋化作用 ,证实γIP 10和Mig是通过CXCR3而发挥作用的。γIP 10和Mig通过CXCR3不仅可诱导趋化作用而且还可诱导GM CSF刺激后的CD34 + 造血干细胞粘附和聚集作用 ,而抗CXCR3mAb能阻断γIP 10和Mig这些功能 ,但不能阻断SDF 1α的作用。γIP 10和Mig能提高整合素(CD49a和CD49b)的表达 ,这在GM CSF刺激后CD34 + 造血干细胞的粘附作用中发挥重要作用。结论　在细胞因子 /趋化因子微环境中 ,CXCR3 γIP 10和 Mig受体配体复合物及GM CSF对CD34 + 造血干细胞分化成淋巴干细胞和髓系干细胞以及后来的免疫 /炎症细胞的生理和病理过程起特别重要作用。这些过程包括CD34 + 造血干细胞的迁移、再定位、分化和成熟。Objective To investigate CXCR3 expression on CD34+ hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor. Methods Using flow cytometry, real time quantitative reverse transcription (RT)-PCR assay, and its ligand γIP-10 and Mig-induced chemotaxis and adhesion assay. Results CXCR3 was expressed on GM-CSF-stimulated, but not freshly isolated, CD34+ hematopoietic progenitors from human cord blood. Freshly isolated CD34+ progenitors expressed low level CXCR3 mRNA, but this expression was highly up-regulated by GM-CSF.γIP-10 and Mig induced GM-CSF stimulated CD34+ progenitor chemotaxis via CXCR3 documented by the fact that anti-CXCR3 mAb blocks γIP-10 and Mig-induced CD34+ progenitor chemotaxis. These chemotactic attracted CD34+ progenitors were colony-forming unit-granulocyte macrophages.γIP-10 and Mig also induced GM-CSF-stimulated CD34+ progenitor adhesion via CXCR3, confirmed by the observation that anti-CXCR3 mAb blocks these functions of γIP-10 and Mig, but not of SDF-1α. γIP-10 and Mig-induced integrin (CD49a and CD49b) up-regulation plays crucial role in adhesion of GM-CSF-stimulated CD34+ progenitors. Conclusion CXCR3-γIP-10 and-Mig receptor-ligand pairs as well as the effects of GM-CSF on them may be especially important in cytokine/chemokine environment for the physiological and pathophysiological events of differentiation of CD34+ hematopoietic progenitors into lymphoid and myeloid stem cells, subsequently immune/inflammatory cells. These processes are including transmigration, relocation, differentiation and maturation of CD34+ hematopoietic progenitors.

关 键 词：抗原 CD34 造血干细胞 胎血 CXCR3 趋化作用 粘附作用 

分 类 号：R331.1[医药卫生—人体生理学] R392.11[医药卫生—基础医学]