活化的巨噬细胞介导的胰岛异种移植排异反应与细胞因子表达上调的关系

摘要

Objective Our previous study has shown that porcine antigen-primed and CD4 + T cells activated macrophages are capable of the ecognition and rejection of porcine xenografts but not mouse allografts, and therefore suggested the involvement of signaling between the graft and macrophages in this specific graft recognition and destruction. Methods NOD-SCID mice were transplanted with fetal pig pancreatic fragment (FPP) before adoptive transfer with exogenous macrophages isolated from rejecting FPP xenografts of BALB/c recipient mice. The exogenous macrophages were tracked by Ly5.1 surface antigen or via CSFE staining. Gene expression of CCR2 and CCR5 and their chemokines in transplanted FPP xenografts was evaluated by real-time PCR. Results After the adoptive transfer, recently transplanted but not established FPP xenografts were rejected by exogenous activated macrophages. In the meantime, greater level of chemokine gene expression was detected in recently-transplanted compared with the established xenografts. Furthermore, expression of both CCR2 and CCR5 genes was enhanced significantly in activated macrophages when compared with non-activated macrophages. Conclusion Upregulated chemokines were associated with macrophage recruitment and destruction of islet xenografts.%目的:笔者以往的实验证明与猪抗原接触过并被CD4+T淋巴细胞激活的巨噬细胞能识别、排斥猪的异种移植物,但不会排斥鼠的同种移植物,这表明在这种特异性移植物免疫识别及破坏过程中移植物及巨噬细胞之间存在着信号联系.方法:在免疫过继转移之前,将胎猪的胰腺碎片移植到非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)鼠.再从移植了胎猪的胰腺碎片(FPP)并发生排斥反应的受体Balb/c鼠身上分离出巨噬细胞,将这些外源性巨噬细胞植入NOD/SCID鼠.这些外源性的巨噬细胞通过Ly5.1表面抗原或通过CSFE染色标记来追踪.在移植了FPP异种移植物以后的CCR2,CCR5及它们的趋化因子的基因表达可通过实时PCR来评估.结果:形成免疫过继后较早移植的异种移植物出现了免疫排斥,而不是建立免疫过继较长时间后再移植FFP的NOD/SCID鼠.同时,前者可检测出更高水平的趋化因子的基因表达.而且,与未激活的巨噬细胞比较,已经激活的巨噬细胞CCR2,CCR5基因的表达增强更为明显.结论:趋化因子的上调与巨噬细胞的聚集、胰岛移植物的破坏有关.