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Reactivation of cytomegalovirus after lung transplantation : a basic and experimental study in rats.

肺移植后巨细胞病毒的再激活：大鼠的基础和实验研究。

基本信息

批准号：
04454340
负责人：
YAGYU Kuniyoshi
金额：
$ 4.22万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

Cytomegalovirus (CMV) infection is a serious complication and sometimes fatal in patients after bone marrow, heart and lung transplantation. In most of the cases, the cause of CMV infection is reactivation of latent virus in the donor organ or in the recipient. The objective of this study was to investigate the mechanism of reactivation of latent CMV after lung transplantation. MATERIALS & METHODS : For the purpose of this study, we established an animal model of CMV infection in rats. We studied interaction between chronic rejection response and rat CMV (RCMV) infection using this model. Orthotopic left lung transplantation was performed in a MHC different rat strain combination (Brown Norway/Lewis), and high dosage cyclosporing (25 mg/kg/day i.m.) was given on dat 2,3 and 4 inducing permanent acceptance of lung allografts. Four months afetr the transplantation, acute RCMV infection was induced by inoculation of 10^5 pfu of RCMV,and rats were killed on day 7 and 21 after the infection. We studied distribution pattern of RCMV antigens in various organs immunohistochemically. RESULTS : 1.In allotransplants 21 days after RCMV infection, 2/3 of the lung allografts showed histological change of chronic rejection and bronchiolitis obliterans. 2.Strongly RCMV antigens positive cells were detected in this lesion. 3.The histological change of bronchiolitis obliterans distributed unevenly, and RCMV antigens positive cells were not observed in other area without histological change of chronic rejection or bronchiolitis obliterans. CONCLUSINS : It seemed that chronic rejection response was an inducing factor of the reactivation of latent CMV.It was also suggested that CMV infection playd an important role in the development of histological change of bronchiolitis obliterans after lung transplantation.

巨细胞病毒（CMV）感染是骨髓、心脏和肺移植后的严重并发症，有时甚至致命。在大多数情况下，CMV感染的原因是供体器官或受体中潜伏病毒的再激活。本研究的目的是探讨肺移植术后潜伏期巨细胞病毒再激活的机制。材料与方法：建立巨细胞病毒感染大鼠模型。我们利用该模型研究了慢性排斥反应与大鼠巨细胞病毒（RCMV）感染之间的相互作用。在MHC不同大鼠品系组合（Brown Norway/刘易斯）中进行原位左肺移植，并在24小时内给予高剂量环孢菌素（25 mg/kg/天i. m.）诱导肺同种异体移植物的永久接受。移植后4个月，通过接种10^5 pfu的RCMV诱导急性RCMV感染，并在感染后第7天和第21天处死大鼠。用免疫组织化学方法研究了RCMV抗原在各器官中的分布规律。研究结果：1.RCMV感染后21天，2/3的移植肺出现慢性排斥反应和闭塞性细支气管炎的组织学改变。2. RCMV抗原阳性细胞。3.闭塞性细支气管炎的组织学改变分布不均匀，在无慢性排斥反应或闭塞性细支气管炎组织学改变的其他区域未观察到RCMV抗原阳性细胞。结论：提示慢性排斥反应可能是潜伏期CMV再激活的诱发因素，CMV感染在肺移植后闭塞性细支气管炎组织学改变的发生中起重要作用。