Yonemitsu Y, Nakagawa K, Tanaka S, Mori R, Sugimachi K, Sueishi K
Department of Pathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Lab Invest. 1996 Apr;74(4):723-36.
Inflammatory abdominal aortic aneurysm (IAAA) is histopathologically characterized by extensive adventitial fibrosis, mononuclear cell infiltration with lymph follicle formation, and severe atheromatous changes in the aneurysmal wall. We previously reported a frequent prevalence and immediate early gene expression of human cytomegalovirus (CMV) in IAAA by solution-phase PCR and reverse transcription PCR, respectively, and suggested that this virus might play a role in chronic inflammatory reaction in IAAA. To evaluate the pathogenic role of CMV infection, the frequency and distribution of CMV infected cells in IAAA were examined by in situ PCR, and compared with those in atherosclerotic aneurysms (AA) and control cases with minimal atherosclerotic changes. Human leukocyte antigen (HLA)-DR was simultaneously evaluated as a marker for immune response related to CMV infection. Immediate early gene expression was also detected by reverse transcription PCR and in situ hybridization, to certify whether the CMV infection in IAAA is active or latent. In the fibrously thickened adventitia of IAAA, CMV infected cells and HLA-DR-positive cells were more frequently encountered than in that of AA and control cases (p < 0.01). CMV infected cells were largely identified as macrophages, fibroblasts, endothelial cells, and lymphocytes. The expression of CMV immediate early mRNA, which suggests an active infection inducing active inflammatory reaction, was detected in most of the macrophages, endothelial cells, and fibroblasts. Our results strongly suggest that frequent and active infection of CMV in IAAA plays a significant role in the induction and acceleration of chronic inflammatory reaction in aortas of IAAA.
炎性腹主动脉瘤(IAAA)的组织病理学特征为广泛的外膜纤维化、伴有淋巴滤泡形成的单核细胞浸润以及瘤壁严重的动脉粥样硬化改变。我们之前分别通过液相PCR和逆转录PCR报道了IAAA中人类巨细胞病毒(CMV)的高患病率和即刻早期基因表达,并提示该病毒可能在IAAA的慢性炎症反应中起作用。为评估CMV感染的致病作用,通过原位PCR检测了IAAA中CMV感染细胞的频率和分布,并与动脉粥样硬化性动脉瘤(AA)和动脉粥样硬化改变轻微的对照病例进行比较。同时评估人类白细胞抗原(HLA)-DR作为与CMV感染相关的免疫反应标志物。还通过逆转录PCR和原位杂交检测即刻早期基因表达,以确定IAAA中的CMV感染是活跃还是潜伏。在IAAA纤维增厚的外膜中,CMV感染细胞和HLA-DR阳性细胞比AA和对照病例中更常见(p<0.01)。CMV感染细胞主要鉴定为巨噬细胞、成纤维细胞、内皮细胞和淋巴细胞。在大多数巨噬细胞、内皮细胞和成纤维细胞中检测到CMV即刻早期mRNA的表达,这表明存在活跃感染并诱导活跃的炎症反应。我们的结果强烈提示,IAAA中CMV的频繁和活跃感染在IAAA主动脉慢性炎症反应的诱导和加速中起重要作用。