[FTY720-induced lymphocyte apoptosis inhibits acute graft versus host disease in rat small bowel transplantation].
OBJECTIVE
To investigate the effect and mechanism of FTY720 on acute graft versus host disease (GVHD) in rat small bowel transplantation (SBTx).


METHODS
Heterotopic SBTx was performed using a parent (WF)-into-F1 (WFxACI) rat combination. Recipient rats were divided into experimental group (n=6) and control group (n=6). Rats in the experimental group were administered with FTY720 at 0.5 mg/kg for 14 days. Lymphocyte apoptosis in the liver and the mucosa of intestine and graft was detected by TUNEL and flow cytometry 15 days after transplantation. Recipient survival and lymphocyte apoptosis were compared between the two groups.


RESULTS
Recipients in the control group died of GVHD after a mean survival time of (16+/-2.1) days. FTY720-treated recipients had a significantly longer survival (>100 days). After administration of FTY720, the percentage of apoptotic lymphocytes was significantly increased in the graft as compared to that in the control group by flow cytometry. The ratio of apoptotic lymphocyte in the liver and graft was also significantly higher in the experimental group by TUNEL.


CONCLUSIONS
FTY720 effectively induces the lymphocyte apoptosis, inhibits the lesion of target tissues by GVHD, and prolongs the recipient survival.
Song
Jing-Hai
JH
Department of Complementary and Alternative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Ito
Toshinori
T
Wei
Jun-Min
JM
Huang
Mei-Xiong
MX
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000068876:Fingolimod Hydrochloride; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000637:transplantation*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016042:Transplantation, Heterotopic
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine