Liang Ting-bo, Xu Dong-yu, Zheng Shu-sen, Li Jian-hua, Liu Zhi-qiang, Fan Shang-da
Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China.
Zhonghua Wai Ke Za Zhi. 2003 Jan;41(1):19-22.
To study the real effect of IL-15, a kind of T lymphocyte activators which were derived from lymphocytes, on the acute rejection process in heart and liver transplantation in rats.
Male (body weight 200 - 250 g) 1A (RT1(a)) and LEW (RT1(l)) rats were selected as donors and recipients, respectively. Heterotopic heart transplantation (in abdomen) and orthotopic liver transplantation were performed as the acute rejection model group (experimental group); LEW (RT1(l))-->LEW (RT1(l)) as donors and recipients to establish isografts transplantation as the control group. Animals were sacrificed on day 1, 3, 5, 7 and graft specimens were collected. Microarray, immunohistochemistry and Western-blotting methods were used to detect the expressions of IL-15, IL-2 and IFN-gamma, etc. 48 rats were divided evenly into two groups and each time-point consisted of 6 rats.
Acute rejections which were clarified by pathological findings and animal manifestations were found 3 days after operation in the experimental group. The early expression of IL-15 was found on endothelial cells in allografts 1 day after operation in contrast to IL-2, which expressed lately and only be found on inflammatory cells including lymphocytes and Kupffer cells 3 days after graft implantation. The result of INF-gamma was the same as that of IL-2.
IL-15 appeared earlier in heart and liver allografts than IL-2 and IFN-gamma in rat acute rejection model, and the expression site differed from the later two. IL-15 participated in acute rejection reaction earlier in this process and the pathway may be different from IL-2 and IFN-gamma. Early blocking this pathway combined with other blockade would have a promising result in control of the progression of acute rejection.
研究一种来源于淋巴细胞的T淋巴细胞激活剂白细胞介素-15(IL-15)对大鼠心脏和肝脏移植急性排斥反应过程的实际影响。
选用雄性(体重200 - 250 g)1A(RT1(a))大鼠和LEW(RT1(l))大鼠分别作为供体和受体。进行异位心脏移植(在腹部)和原位肝脏移植作为急性排斥模型组(实验组);以LEW(RT1(l))→LEW(RT1(l))作为供体和受体建立同基因移植作为对照组。在第1、3、5、7天处死动物并采集移植器官标本。采用基因芯片、免疫组织化学和蛋白质印迹法检测IL-15、IL-2和干扰素-γ等的表达。48只大鼠平均分为两组,每个时间点有6只大鼠。
实验组术后3天出现经病理检查和动物表现证实的急性排斥反应。与IL-2相比,移植术后1天在同种异体移植器官的内皮细胞上发现IL-15的早期表达,而IL-2表达较晚,仅在移植后3天在包括淋巴细胞和库普弗细胞在内的炎性细胞上发现。干扰素-γ的结果与IL-2相同。
在大鼠急性排斥模型中,IL-15在心脏和肝脏同种异体移植中比IL-2和干扰素-γ出现更早,且表达部位与后两者不同。在此过程中,IL-15更早地参与急性排斥反应,其途径可能与IL-2和干扰素-γ不同。早期阻断该途径并联合其他阻断措施在控制急性排斥反应进展方面可能会有良好效果。