CAJ | 학술논문

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1×107个C57BL/6（H2b）小鼠来源的骨髓细胞和5×106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。
목적탐토S1P수체격동제FTY720재이기인조혈간세포이식후급성이식물항숙주병（acute graft-versus-host disease，aGVHD）진정중적작용급기가능적궤제。방법 BALB/c （H2d）수체서접수750 cGy전신성치사성복조，4 h후통과미정맥주사적방법수주1×107개C57BL/6（H2b）소서래원적골수세포화5×106개전비세포，건립aGVHD모형。종이식전제1천（ day 1）지이식후제4천（day 4）매천급소서복강주사FTY720（3 mg/kg）혹등체적대조조용제，관찰소서생존。이식후제4천채용류식세포술검측량조소서적비장、간장、폐화소장4개장기중적면역세포적표형。결과FTY720능현저연장이기인조혈간세포이식후aGVHD적상관존활；류식세포술결과발현FTY720능현저억제폐화소장중성숙DC적분포。결론 FTY720능현저억제폐화소장중성숙DC분포，종이감경aGVHD。
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 1×107 C57BL/6 (H2b) mice derived bone marrow cells (BMCs) and 5×106 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 re-ceived allogeneic hematopoietic stem cell transplantation .The possible mechanism might be associated with the inhibited distribution of matured DCs in lung and intestines .