G-CSF对白血病细胞表面CXCR4表达及其趋化功能的影响

The effects of G- CSF on the regulation of CXCR- 4 expression and chemotaxis in leukemia cells

目的:观察G-CSF对U937细胞及WEHI-3细胞表面CXCR4表达水平及细胞趋化性的影响,探讨G-CSF对白血病细胞免疫微环境的影响。方法:U937细胞及WEHI-3细胞分别与G-CSF共培养,应用流式细胞仪检测细胞CXCR4的表达,微孔细胞转移试验观察细胞的迁移能力。结果:U937细胞及WEHI-3细胞表面CXCR4表达随G-CSF作用时间的延长可明显降低(P<0.05)。U937细胞及WEHI-3细胞与GCSF共培养后迁移至下室的细胞数较未与G-CSF共培养的细胞明显减少(P<0.05)。未与G-CSF共培养的U937和WEHI-3细胞具有向SDF-1迁移的能力(P<0.05)。结论:G-CSF不仅可以降低白血病细胞表面CXCR4的表达,同时可以降低白血病细胞向SDF-1的迁移能力,G-CSF可能通过改变白血病细胞免疫微环境,从而打破白血病细胞免疫逃逸。

Objective： To investigate the effects of granulocyte colony- stimulating factor（ G- CSF） on the regulation of C- X- C chemokine receptor type 4（ CXCR4） expression and chemotaxis in U937 cell and WEHI- 3 cell line. Methods： Co- culture U937 cell and WEHI- 3 cell with G- CSF for 6 hours,12 hours,18 hours,24 hours.Flow cytometer（ FCM） was used to detect the expression of CXCR4,and microporous cell transfer experiment to observe migration ability of U937 cell and WEHI- 3 cell. Results： G- CSF inhibited the expression of CXCR4 in U937 cell and WEHI- 3 cell with extension of time co- culture. After cultured 18 hours with G- CSF,the expression level of CXCR4 decreased to a minimum（ P〈 0. 05）. The cells entered the lower chamber of Transwell were significantly decreased between co- culture 18 hours with G- CSF and without G- CSF（ P〈 0. 05）. Instead,the cell without co- cultur with G- CSF had stronger ability to migrate to the stromal cell- derived factor- 1（ SDF- 1） than that cell cultured with G- CSF（ P〈 0. 05）. Conclusion： G- CSF not only down- regulated expression of cell surface CXCR4 but also inhibited the cell migration to SDF- 1 in U937 cell and WEHI- 3 cell. G- CSF might suppress the immune escape of leukemia cells by regulating the immune micro- environmental of bone marrow,which may provide a new strategy for treatment of leukemia.