RANTES expression in small intestine grafts during allograft rejection of rats / 中国组织工程研究

ABSTRACT

BACKGROUND: AIIograft rejection is the greatest obstacle that influences graft function and survival, and the diagnosis and treatment of small intestine transplantation rejection are particularly difficult.OBJECTIVE: To explore the significance of chemokine receptor antagonist, Met-RANTES, in small intestine transplantation rejection, and the effects of tacrolimus (FK506) on RANTES expression.DESIGN, TIME AND SETTING: Randomized, controlled animal experiment was performed at the Department of General Surgery, the 451 Hospital of Chinese PLA; Laboratory of Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University of Chinese PLA; and Electronic Microscope Center, School of Basic Medicine, Fourth Military Medical University of Chinese PLA between September 2003 and March 2005.MATERIALS: A total of 72 healthy adult male SD rats (donor) and 72 healthy adult male Wistar rats (recipient) were included for heterotopic small intestine transplantation.METHODS: Heterotopic small intestine transplantation was performed. All recipients were divided into four groups (n=18): intact control group: Wistar rats as controls with no surgery; isotransplantation group: Wistar--,Wistar; allotransplantation untreated group: SD→Wistar, with no immunosuppressive agent; allograft allotransplantation and FK-506 group: SD→Wistar + FK-506 (1 mg/kg per day, i.m. for 7 days). The grafts were sampled on postoperative days 3, 5 and 7 and were examined pathologically. Successive quantitative measurement was conducted to detect the expression of graft RANTES with immunofluorescence staining and laser scanning confocal microscope technique.MAIN OUTCOME MEASURES: The pathological changes of grafts in each group; RANTES expressions in small intestine grafts of rats in each group at different time points; inhibition of FK-506 on RANTE expression.RESULTS: Postoperatively, 72 Wistar rats (recipient) were involved in the final analysis. The pathological changes of the allotransplantation untreated group rats were consistent with the criteria of mild, moderate and severe rejection on postoperative days 3, 5 and 7, respectively. No obvious rejection was found in the rats of FK506 group and isotransplantation group on the postoperative days 3, 5 and 7. Expression of intragraft RANTES of allotransplantation untreated group rats was significantly greater than the other three groups (P<0.01). The dynamic change and the process of acute rejection showed positive correlation. Expression of intragraft RANTES in FK-506 treated group was significantly less than other three groups without FK-506 (P<0.01).CONCLUSION: RANTES positive cells play an important role in small intestine allograft rejection. Dynamic observation on expression of intragraft RANTES may act as a predicator for diagnosing acute allograft rejection.