CAJ | 학술논문

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CXCR3 mRNA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CXCR3 mAb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。
목적연구GM-CSF유도인제혈CD34+조혈간세포상CXCR3적표체。방법채용류식세포의，실시정량역전록PCR（RT-PCR）분석，급기배체γIP-10화Mig유도적추화화점부작용분석。결과 CXCR3야표체재수GM-CSF자격후적CD34+조혈간세포상，단타재신선분리적CD34+조혈간세포상불표체。응용실시정량역전록PCR기술검측신선분리적CD34+조혈간세포유교저수평적CXCR3 mRNA표체，이GM-CSF능상조CXCR3적표체。용항CXCR3단극륭항체（mAb）능조단γIP-10화Mig유도적조혈간세포추화작용，증실γIP-10화Mig시통과CXCR3이발휘작용적。γIP-10화Mig통과CXCR3불부가유도추화작용이차환가유도GM-CSF자격후적CD34+조혈간세포점부화취집작용，이항CXCR3 mAb능조단γIP-10화Mig저사공능，단불능조단SDF-1α적작용。γIP-10화Mig능제고정합소（CD49a화CD49b）적표체，저재GM-CSF자격후CD34+조혈간세포적점부작용중발휘중요작용。결론재세포인자/추화인자미배경중，CXCR3-γIP-10화-Mig수체배체복합물급GM-CSF대CD34+조혈간세포분화성림파간세포화수계간세포이급후래적면역/염증세포적생리화병리과정기특별중요작용。저사과정포괄CD34+조혈간세포적천이、재정위、분화화성숙。
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.