title: Effects of long-term administration of low-dose FTY720 on survival of murine cardiac allograft.
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.
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Surgery, Tianjin Nankai Hospital, Tianjin, 300100, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Liang
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College of Shihezi University, Shihezi, 832008, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Dou
authors.initials: D
authors.lastname: Lei
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Long
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yifa
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China. Zhupeng@medmail.com.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China. Chenxp@medmail.com.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011409:Propylene Glycols / Q000008:administration & dosage*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine