PATHOGENESIS OF BILE DUCT INJURY IN AIDS

艾滋病胆管损伤的发病机制

• 批准号: 3240953
• 负责人: MICHAEL A GERBER
• 金额: $ 12.16万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-15 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3240953
• 关键词: AIDS; Macaca; bile ducts; biliary tract disorder; cellular pathology; disease /disorder model; electron microscopy; enzyme linked immunosorbent assay; histochemistry /cytochemistry; human tissue; immunopathology; liver disorder; medical complication; molecular pathology; monocyte; secondary infection

A wide spectrum of diseases of the liver and biliary tree has been observed in patients with AIDS and contributes significantly to the morbidity and mortility in this population. Similar alterations have been described in rhesus macaques with simian acquired immunodeficiency syndrome (SAIDS) which represents an excellent model of the human disease. Preliminary studies of man and rhesus macaques infected with human or simian immunoideficiency virus (HIV, SIV) identified characteristic necroinflammatory, degenerative, and hyperplastic lesions of the bile ducts, so-called "non-suppurative cholangitis." It is not clear whether these bile duct alterations are directly or indirectly related to infection by HIV/SIV or to secondary complications of AIDS/SAIDS such as superinfections by other infectious agents. It is our long-term objective to elucidate the cellular and molecular mechanism of bile duct injury in AIDS. Based on our preliminary immunopathologic studies, we postulate that bile duct damage in AIDS/SAIDS is mediated by immunologic mechanisms. To evaluate this hypothesis, the liver of rhesus monkeys (Macac alpha mulatta) will be analyzed by quantitative morphologic methods at predetermined time intervals after experimental infection with two strains of SIV with different pathogenic potentials. SIV and other viruses (cytomegalovirus and Epstein-Barr virus) will be localized in the liver of infected monkeys by immunohistochemical and in situ hybridization methods. Bile duct damage will be quantitated by light and electron microscopic morphometry. HLA class I and class II antigens, IgA, and cytokeratins will be demonstrated in the bile ducts by immunohistochemical methods at the light and ultrastructural levels. The mononuclear cell subpopulations infiltrating the portal tracts around the bile ducts will be enumerated by immunomorphometric methods. These quantitative data will be correlated with the duration and course of experimental SIV infections, the state of the disease, and the immunologic and virologic status of the rhesus macaques with SAIDS. The observations will also be compared with the bile duct disease in patients with AIDS. We hope that these studies will lead to a better understanding of bile duct injury and to a more rational management of liver disease in patients with AIDS.

肝脏和胆汁树的各种疾病已经 在艾滋病患者中观察到 该人群的发病率和死亡率。 类似的改变 已在鼠尾草猕猴中描述了 免疫缺陷综合征（所说）代表 人类疾病的出色模型。 人的初步研究 和感染了人类或猿猴的恒河猕猴 免疫智能病毒（HIV，SIV）确定了特征 坏死性，退化性和增生性病变 胆管，所谓的“非支持性胆管炎”。 还不清楚 这些胆管改变是直接还是间接的 与HIV/SIV感染或次要并发症有关 艾滋病/说，诸如其他传染剂的超级感染。 它 是我们阐明细胞和分子的长期目标 艾滋病中胆管损伤的机理。 基于我们的初步 免疫病理学研究，我们假设胆管损伤 艾滋病/说是由免疫机制介导的。 到 评估这一假设，即恒河猴的肝脏（Macac alpha Mulatta）将通过定量形态学方法进行分析 实验感染后的预定时间间隔 具有不同致病电位的两个SIV菌株。 siv和 其他病毒（巨细胞病毒和爱泼斯坦 - 巴尔病毒）将是 局部在受感染猴子的肝脏中 免疫组织化学和原位杂交方法。 胆管 损坏将通过光和电子显微镜定量 形态计量学。 HLA I类和II类抗原，IgA和 细胞角蛋白将在胆管中通过 在光和超微结构上的免疫组织化学方法 水平。 单核细胞亚群渗透 胆汁管周围的门户区将被列举 免疫法计量学方法。 这些定量数据将是 与实验SIV的持续时间和过程相关 感染，疾病状态以及免疫学和 恒河猕猴的病毒学状态。 这 也将将观察结果与胆管疾病进行比较 艾滋病患者。 我们希望这些研究将导致 更好地了解胆管损伤和更合理的 艾滋病患者的肝病治疗。