摘要
目的探讨S1P受体激动剂FTY720在异基因造血干细胞移植后急性移植物抗宿主病（acute graft-versus-host disease，aGVHD）进程中的作用及其可能的机制。方法 BALB/c （H2d）受体鼠接受750 cGy全身性致死性辐照，4 h后通过尾静脉注射的方法输注1×10^7个C57BL/6（H2b）小鼠来源的骨髓细胞和5＆#215;106个全脾细胞，建立aGVHD模型。从移植前第1天（ day 1）至移植后第4天（day 4）每天给小鼠腹腔注射FTY720（3 mg/kg）或等体积对照组溶剂，观察小鼠生存。移植后第4天采用流式细胞术检测两组小鼠的脾脏、肝脏、肺和小肠4个脏器中的免疫细胞的表型。结果FTY720能显著延长异基因造血干细胞移植后aGVHD的相关存活；流式细胞术结果发现FTY720能显著抑制肺和小肠中成熟DC的分布。结论 FTY720能显著抑制肺和小肠中成熟DC分布，从而减轻aGVHD。
Objective To investigate the role of FTY720, an agonist of the sphingosine 1-phos-phate （S1P） receptor, in acute graft-versus-host disease （aGVHD） caused by allogeneic hematopoietic stem cell transplantation and to further elucidate its possible mechanism .Methods BALB/c （ H2 d ） recipient mice were given whole body lethal irradiation （750 cGy） for 4 hours.A mouse model of aGVHD was estab-lished by intravenously injecting recipient mice with 1×10^7 C57BL/6 （H2b） mice derived bone marrow cells （BMCs） and 5＆#215;106 whole splenic cells.FTY720 （3 mg/kg） was intraperitoneally injected into recipient mice from the day before allogeneic bone marrow transplantation （ allo-BMT） to day 4 thereafter to monitor the survival rate .The mice in control group were perfused with equal volume of control reagent .Fluores-cence-activated cell sorting （ FACS） was used to analyze the phenotypes of immune cells in spleen , liver, lung as well as intestines of mice on the fourth day of allo-BMT with or without FTY720 treatment. Results FTY720 significantly prolonged overall survival in mice with allo-BMT induced aGVHD .FACS analysis showed that FTY720 significantly inhibited the distribution of matured dendritic cells （ DCs） in lung and small intestines .Conclusion FTY720 could significantly alleviate the symptom of aGVHD in mice received allogeneic hematopoietic stem cell transplantation .The possible mechanism might be associated with the inhibited distribution of matured DCs in lung and intestines .
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2014年第7期498-502,共5页
Chinese Journal of Microbiology and Immunology
