ALVEOLAR MACROPHAGES AND DEFENSE OF THE LUNG IN AIDS

肺泡巨噬细胞和艾滋病中肺部的防御

• 批准号: 3362161
• 负责人: OFRA K WEINBERGER
• 金额: $ 17.16万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3362161
• 关键词: HIV infections; MHC class II antigen; alveolar macrophages; cell adhesion; electroporation; gene expression; genetic mapping; genetic transcription; genetic translation; glycoproteins; human tissue; immunocytochemistry; interleukin 1; lysozyme; messenger RNA; molecular cloning; surface antigens; transfection; tumor necrosis factor alpha

The macrophage plays s central role in AIDS pathogenesis not only by being susceptible to HIV infection but also by serving as a major reservoir for the dissemination of virus in infected individuals. The alveolar macrophage is one of the principle cell types involved in the immune defense mechanisms of the lung. Based on our understanding of the macrophage as a critical cell in the induction of cellular immune responses, it is of great importance to study the nature of the interaction of the virus with human alveolar macrophages. The goal of this research proposal is the establishment of a system, utilizing primary human alveolar macrophages, for the analyses of macrophage function and gene expression following the introduction of HIV genes. This will involve the optimization of conditions for transfection of these cells and the transfection into alveolar macrophages of sub-genomic viral fragments as well as isolated HIV genes. Subsequently, the effect of specific viral gene expression on the expression of macrophage products and cell surface markers will be analyzed; specifically, the expression of major histocompatibility complex (MHC) class II antigens, tumor necrosis factor (TNF), interleukin- 1 (IL-1), the adherence molecules of LFA-1, Mac-1, and p150/95, FcRI and FcRII, and lysozyme. The mechanism of the modulation will be analyzed, the target of the effect will be defined, and the region(s) of functional importance in the viral gene will be determined. The activities of lymphocytotrophic and monocytotropic viruses will be compared in regard to their ability to perturb alveolar macrophage physiology. These studies will provide insight into mechaniss underlying the profound immunodeficiency which is central in AIDS pathogenesis.

巨噬细胞不仅在艾滋病发病机制中起核心作用， 容易感染艾滋病毒， 在受感染的国家传播病毒的主要宿主 个体 肺泡巨噬细胞是其中的主要细胞之一 参与肺部免疫防御机制的类型。 基于 我们对巨噬细胞作为一个关键细胞的理解， 诱导细胞免疫反应，这是非常重要的 研究病毒与人类相互作用的本质 肺泡巨噬细胞 这项研究计划的目标是 建立一个系统，利用原代人肺泡 巨噬细胞，用于巨噬细胞功能和基因分析 在引入HIV基因后的表达。 这将 包括优化转染这些细胞的条件， 细胞和转染到肺泡巨噬细胞的亚基因组 病毒片段以及分离的HIV基因。 随后 特异性病毒基因表达对 分析巨噬细胞产物和细胞表面标志物; 特别是主要组织相容性复合体的表达 (MHC)II类抗原，肿瘤坏死因子（TNF），白细胞介素- 1（IL-1）、LFA-1、Mac-1和p150/95的粘附分子， FcRI和FcRII以及溶菌酶。 调制机制将 通过分析，确定了影响的目标， 病毒基因中的重要功能区将被 测定 淋巴细胞和单核细胞的活性 将比较病毒干扰 肺泡巨噬细胞生理学 这些研究将提供洞察力 深入研究免疫缺陷的机制， 艾滋病发病机制的核心。