Xiong Hai-Bo, Huang Zu-Fa, Ye Qi-Fa, Xia Sui-Sheng
Institute of Transplantation, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2007 Feb;32(1):41-6.
To observe the effect of FTY720 and ICAM-1 mAb mono and combination therapy in mouse-to-rat cardiac xenotransplantation.
Cardiac xenotransplantation was performed in abdominal site with micro-surgical technique. Recipients with xenografts were treated with different doses of FTY720 and/or ICAM-1 mAb. Graft survival, histopathology, infiltration of CD4+, and CD8+ T cells and levels of serum IL-2, IFN-gamma, IL-4, and IgM were investigated.
Survival time of xenografts was (2.75+/- 0.43)d in the controls, survival of grafts treated with ICAM-1 mAb did not significantly improve. Treatment with large dose FTY720 led to a survival of (4.25+/- 0.71)d (P<0.01). Combination therapy with large dose FTY720 and ICAM-1 mAb achieved a significant prolongation of graft survival with (10.25+/- 2.12)d (P<0.01). Levels of serum IL-2, IFN-gamma and rat-anti-mouse IgM decreased in the combined therapy group. Pathologic lesion and infiltration of T cells in xenografts showed mitigated in the large dose combined therapy group. There was a significant negative correlation between the antibody level and the graft survival time (R=-0.754, P<0.01).
The combined therapy of FTY720 and ICAM-1 mAb can achieve a significant effect in the prolongation of heart xenograft survival and inhibition of xenoantibodies.
观察FTY720与细胞间黏附分子-1单克隆抗体（ICAM-1 mAb）单药及联合治疗对小鼠到大鼠心脏异种移植的影响。
采用显微外科技术在腹部进行心脏异种移植。对接受异种移植的受体给予不同剂量的FTY720和/或ICAM-1 mAb治疗。观察移植物存活情况、组织病理学变化、CD4⁺和CD8⁺ T细胞浸润情况以及血清白细胞介素-2（IL-2）、干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）和免疫球蛋白M（IgM）水平。
对照组移植物存活时间为（2.75±0.43）天，ICAM-1 mAb治疗组移植物存活时间无明显改善。大剂量FTY720治疗使移植物存活时间达到（4.25±0.71）天（P<0.01）。大剂量FTY720与ICAM-1 mAb联合治疗显著延长了移植物存活时间，为（10.25±2.12）天（P<0.01）。联合治疗组血清IL-2、IFN-γ和大鼠抗小鼠IgM水平降低。大剂量联合治疗组异种移植物的病理损伤和T细胞浸润减轻。抗体水平与移植物存活时间呈显著负相关（R=-0.754，P<0.01）。
FTY720与ICAM-1 mAb联合治疗在延长心脏异种移植物存活时间和抑制异种抗体方面有显著效果。
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