Sugito Kiminobu, Uekusa Shota, Kawashima Hiroyuki, Masuko Takayuki, Furuya Takeshi, Konuma Noriyoshi, Ohashi Kensuke, Inoue Mikiya, Ikeda Taro, Koshinaga Tsugumichi
Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan.
Pediatr Transplant. 2010 Aug;14(5):614-7. doi: 10.1111/j.1399-3046.2010.01295.x. Epub 2010 Feb 28.
We studied the effect of the combined treatment with FK506, FTY720, and ex vivo graft irradiation. Five groups of SBT animals were studied on days 3, 5, and 7 after operation (untreated, FK506, FTY720, FK506 + FTY720, FK506 + FTY720 + irradiation). Indirect immunoperoxidase staining was performed against CD4 and MAdCAM-1. The numbers of CD4 positive cells in allografts were also analyzed by flow cytometry. The graft survival was prolonged in all of the FK506- and FTY720-treated groups. SBT allografts treated by FK506 and FTY720 demonstrated less infiltration of CD4 positive cells, but the irradiation group did not show any effects on its expression. In FK506- and FTY720-treated groups, MAdCAM-1 expression on the HEVs in PPs was up-regulated, and its expression on the ECVs in the LP was down-regulated compared with other allograft groups. Irradiation did not show any effects on MAdCAM-1 expression on both HEVs in PPs and ECVs in LP. FK506 and FTY720 prevented the infiltration of CD4 positive cells, the down-regulation of MAdCAM-1 expression on HEVs in PPs, and the up-regulation of MAdCAM-1 expression on ECVs in LP during the early phase of SBT.
我们研究了FK506、FTY720和体外移植物照射联合治疗的效果。对五组小肠移植（SBT）动物在术后第3、5和7天进行研究（未治疗组、FK506组、FTY720组、FK506 + FTY720组、FK506 + FTY720 + 照射组）。采用间接免疫过氧化物酶染色检测CD4和黏膜地址素细胞黏附分子-1（MAdCAM-1）。还通过流式细胞术分析同种异体移植物中CD4阳性细胞的数量。所有接受FK506和FTY720治疗的组移植物存活时间均延长。FK506和FTY720处理的SBT同种异体移植物中CD4阳性细胞浸润较少，但照射组对其表达没有任何影响。在接受FK506和FTY720治疗的组中，与其他同种异体移植组相比，派氏集合淋巴结（PP）中高内皮微静脉（HEV）上的MAdCAM-1表达上调，而黏膜下层（LP）中外周血管（ECV）上的MAdCAM-1表达下调。照射对PP中HEV和LP中ECV上的MAdCAM-1表达均无影响。在SBT早期，FK506和FTY720可阻止CD4阳性细胞浸润、PP中HEV上MAdCAM-1表达的下调以及LP中ECV上MAdCAM-1表达的上调。
