Kageyama Y, Li X K, Suzuki S, Suzuki H, Suzuki K, Kazui T, Harada Y
First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Ann Thorac Surg. 1998 Jun;65(6):1604-9. doi: 10.1016/s0003-4975(98)00240-9.
Allograft rejection remains a major obstacle to long-term survival in heart transplantation. Recent studies have demonstrated that apoptotic cell death may occur in acute allograft rejection. The purpose of this study was to determine whether apoptotic cell death is involved in rat cardiac allograft rejection through both the perforin/granzyme pathway and the Fas/Fas ligand (Fas-L) pathway.
Groups of Lewis (RT1(1)) rats underwent heterotopic heart transplantation from disparate DA (RT1a) or syngeneic Lewis rats. The cardiac grafts were harvested 1, 3, or 5 days after transplantation and analyzed for apoptotic cell death using DNA nick-end labeling, immunocytochemistry, and electron microscopy. In addition, the expression of granzyme B, perforin, Fas, and Fas-L messenger RNA were analyzed by reverse transcriptase-polymerase chain reaction.
Apoptotic cell death of cardiac myocytes was prominent in allografts on day 5 after transplantation. Fas gene transcripts were constitutively expressed in both syngeneic and allogeneic grafts, whereas expression of Fas-L was only upregulated in allografts with ongoing rejection. Granzyme B and perforin gene expression were also upregulated in allografts with ongoing rejection.
These results suggest that myocyte apoptosis through both the perforin-granzyme pathway and the Fas-Fas-L pathway may be involved in cardiac allograft rejection in rats.
同种异体移植排斥反应仍然是心脏移植长期存活的主要障碍。最近的研究表明，凋亡性细胞死亡可能发生在急性同种异体移植排斥反应中。本研究的目的是确定凋亡性细胞死亡是否通过穿孔素/颗粒酶途径和Fas/Fas配体（Fas-L）途径参与大鼠心脏同种异体移植排斥反应。
将Lewis（RT1(1)）大鼠分组，接受来自不同品系的DA（RT1a）大鼠或同基因Lewis大鼠的异位心脏移植。在移植后1、3或5天收获心脏移植物，使用DNA缺口末端标记、免疫细胞化学和电子显微镜分析凋亡性细胞死亡情况。此外，通过逆转录聚合酶链反应分析颗粒酶B、穿孔素、Fas和Fas-L信使RNA的表达。
移植后第5天，同种异体移植物中心肌细胞的凋亡性细胞死亡明显。Fas基因转录本在同基因和异基因移植物中均持续表达，而Fas-L的表达仅在正在发生排斥反应的同种异体移植物中上调。颗粒酶B和穿孔素基因表达在正在发生排斥反应的同种异体移植物中也上调。
这些结果表明，通过穿孔素-颗粒酶途径和Fas-Fas-L途径的心肌细胞凋亡可能参与大鼠心脏同种异体移植排斥反应。
