Martelius T, Krogerus L, Höckerstedt K, Bruggeman C, Lautenschlager I
Fourth Department of Surgery, Helsinki University Central Hospital, Finland.
Hepatology. 1998 Apr;27(4):996-1002. doi: 10.1002/hep.510270415.
It has been suggested that cytomegalovirus (CMV) infection is involved in allograft rejection. In liver transplantation, it has been suggested that CMV is associated with the development of vanishing bile duct syndrome (VBDS), and persistent CMV has been found in liver grafts that develop chronic rejection. In this experimental study, the effect of rat CMV (RCMV) infection on intragraft changes was investigated in a rat model of acute liver allograft rejection. Liver transplantations were performed in a rat strain combination of PVG (RT1c) --> BN (RT1n). No immunosuppression was given. One group of animals was infected with RCMV Maastricht Strain (10(5) plaque-forming units, intraperitoneally), and another group was left uninfected. The grafts were examined histologically after the rats were killed on postoperative days 7 through 9 at the early phase and days 20 through 30 at the late phase of rejection. Immunohistochemical studies were performed to demonstrate the immunological activation markers major histocompatibility complex class II and interleukin 2 receptors, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and their ligands. RCMV infection was demonstrated from the grafts by culture and direct antigen detection. In liver allografts undergoing acute rejection, CMV significantly increased portal inflammation and caused more severe bile duct damage than in the uninfected grafts. CMV was also linked to the induction of VCAM-1 in the endothelial cells. The ongoing infection was found to vary over time in the different structures of the liver grafts, including the vascular endothelium and bile ducts. Our results support an association between CMV infection and the immunological mechanisms of rejection, as well as the role of CMV in the development of bile duct damage in liver allografts.
有人提出巨细胞病毒（CMV）感染与同种异体移植排斥反应有关。在肝移植中，有人认为CMV与消失性胆管综合征（VBDS）的发生有关，并且在发生慢性排斥反应的肝移植物中发现了持续性CMV。在本实验研究中，在大鼠急性肝同种异体移植排斥反应模型中研究了大鼠巨细胞病毒（RCMV）感染对移植物内变化的影响。肝移植采用PVG（RT1c）→BN（RT1n）大鼠品系组合进行。未给予免疫抑制。一组动物腹腔注射RCMV马斯特里赫特株（10⁵ 空斑形成单位），另一组未感染。在排斥反应早期的术后第7至9天以及晚期的术后第20至30天处死大鼠后，对移植物进行组织学检查。进行免疫组织化学研究以显示免疫激活标志物主要组织相容性复合体II类和白细胞介素2受体、细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）及其配体。通过培养和直接抗原检测从移植物中证实了RCMV感染。在发生急性排斥反应的肝同种异体移植物中，CMV显著增加了门静脉炎症，并且比未感染的移植物导致更严重的胆管损伤。CMV还与内皮细胞中VCAM-1的诱导有关。发现正在进行的感染在肝移植物的不同结构（包括血管内皮和胆管）中随时间变化。我们的结果支持CMV感染与排斥反应的免疫机制之间的关联，以及CMV在肝同种异体移植物胆管损伤发展中的作用。
