目的探讨基质细胞衍生因子受体CXCR4阻断剂AMD3100(plerixafor)单独或与G-CSF联合应用对小鼠脾脏淋巴细胞增殖能力及其对肿瘤细胞杀伤作用的影响。方法以C57BL/6(H-2。)小鼠为供鼠,应用CCK-8分别检测AMD3100、G-CSF、AMD3100联合G-CSF及生理盐水动员后各组供鼠脾脏淋巴细胞经丝裂原诱导的增殖活性,及其与受鼠BALB/C(H-2。)小鼠脾脏淋巴细胞之间的混合淋巴细胞反应;应用LDH释放法检测上述各组供鼠脾脏淋巴细胞对淋巴瘤细胞株Yac-1细胞的杀伤功能。结果与生理盐水对照组(1.86±0.07及1.58±0.15)相比,AMD3100动员组(1.23±0.04及1.18±0.05)、G-CSF动员组(1.19±0.05及1.17±0.04)及AMD3100联合G-CSF动员组(1.11±0.04及1.03±0.04)小鼠脾脏淋巴细胞的增殖能力、对异种抗原的反应能力均降低(P值均〈0.05),AMD3100联合G-CSF动员组较其他各组降低更为明显,差异有统计学意义(P值均〈0.05)。在效靶比为40:1时,AMD3100动员组[(5.69±0.25)%]、G-CSF动员组[(5.63±0.29)%]及AMD3100联合G-CSF动员组[(5.76±0.24)%]小鼠脾脏淋巴细胞对肿瘤细胞的杀伤作用均较生理盐水对照组[(5.98±0.31)%]降低,但差异均无统计学意义(P值均〉0.05)。结论AMD3100单独或与G-CSF联合应用后,小鼠脾脏淋巴细胞的增殖功能及对异种抗原的反应能力降低,而其对肿瘤细胞的杀伤功能未受明显影响,其作用机制有待深入研究。
Objective To investigate the impact of the mobilization with the antagonist of the stromal cell-derived factor receptor CXCR4 ( AMD3100 ) (plerixafor) , granuloeyte-colony-stimulating factor ( G-CSF ) alone and in combination on the proliferation and cytotoxic functions of the routine splenic lymphocytes. Methods C57BL/6(H-2b) mice,as donors,were mobilized by, AMD3100,G-CSF alone or in combination (n = 10 mice in each group) , and phosphate buffered saline (PBS). Then, the proliferation capacity of mu- rine lymphocytes either in response to the phyohemaglutinin (PHA) stimulation or the mixed lymphocytes re- action (MLR) with allo-lymphocytes from the BALB/C( H-2d) mice were detected by CCK-8 method. The cy- totoxic capacity of murine lymphocytes onYac-1 tumor cells was examined by LDH assay. Results The pro- liferation capacity and the responsiveness to alloantigen of the lymphocytes derived from the mice spleen mobilized by AMD3100(1.23 ±0.04 and 1.18±0.05) ,G-CSF(1.19 ±0.05 and 1.17±0.04) alone or in com- bination ( 1.11 ±0.04 and 1.03 ±0.04) were significantly lower than those by PBS control ( 1.86 ± 0.07 and 1.58 ± 0.15 ) ( P 〈 0.05 ), and those combinatin of AMD 3100 and G-CSF group were significantly lower than in other groups ( P 〈 0.05 ). At the effeetor-target ration of 40: 1, the cytotoxie capacity of murine lymphocytes in above mobilization groups [( 5.69 ±0.25 ) %, ( 5.63 ± 0.29 ) % and ( 5.76 ± 0.24 ) % ] was lower than in control group [ ( 5.98± 0.31 ) % ], but no statistically significant difference ( P 〉 0.05 ). Conclusion Both the proliferation capacity and the responsiveness to alloantigen of the murine lymphocytes decreasessignificantly after the mobilization with AMD3100, G-CSF alone or in combination, whereas no significant al- ternations are demonstrated on the cytotoxic capacity of murine lymphocytes. Further studies are needed to clarify the underlying mechanisms.