Effects of long-term administration of low-dose FTY720 on survival of murine cardiac allograft |
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Authors: | Qi Cheng Dan Li Huifang Liang Hongqiang Yang Dou Lei Dan Gao Xin Long Yifa Chen Peng Zhu Xiaoping Chen |
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Institution: | Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China. chengqi1983@qq.com |
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Abstract: | This study examined the effect of long-term administration of low-dose FTY720 on survival of murine cardiac allograft and
the possible mechanism. Murine models of abdominal heterotopic heart transplantation were established. Low-dose FTY720 (0.3
mg/kg) was administrated to the animals 4 days before the transplantation of cardiac allografts until the occurrence of rejection
or the observation terminals. The animals without FTY720 treatment and those with syngeneic cardiac grafts transplanted served
as controls. The mean survival time (MST) of grafts, and T lymphocyte subsets in grafts, peripheral blood and lymphoid organs
were measured by histopathological examination or flow cytometry, and compared among groups. The results showed that the MST
of allografts in FTY720-treated mice was more than 40 days, significantly longer than that in the untreated group (MST=8 days,
P<0.01). After the long-term administration of FTY720, the proportion of CD4+ and CD8+ lymphocytes in peripheral blood was diminished significantly, but the proportion of CD4+ lymphocytes was increased in mesenteric lymph nodes (MLNs) and spleen. Immunofluorescence staining revealed that the infiltration
of CD4+ and CD8+ lymphocytes in allografts was significantly inhibited after long-term administration of low-dose FTY720. It was concluded
that low-dose long-term administration of FTY720 could promote T lymphocytes in lymphatic organs and decrease their infiltration
in allografts, resulting in the inhibition of rejection and the long-term survival of allografts. |
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Keywords: | FTY720 immunosuppressant heart transplantation rejection lymphocyte |
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