ALVEOLAR MACROPHAGES AND DEFENSE OF THE LUNG IN AIDS

巨噬细胞不仅在艾滋病发病机制中发挥着核心作用 由于容易感染艾滋病毒，而且还作为 感染者体内病毒传播的主要储存库 个人。 肺泡巨噬细胞是主要细胞之一 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，非常重要 研究病毒与人类相互作用的本质 肺泡巨噬细胞。 本研究计划的目标是 建立一个系统，利用原始人类肺泡 巨噬细胞，用于分析巨噬细胞功能和基因 引入HIV基因后的表达。 这将 包括转染条件的优化 细胞和亚基因组的肺泡巨噬细胞的转染 病毒片段以及分离的艾滋病毒基因。 随后， 特定病毒基因表达对表达的影响 将分析巨噬细胞产物和细胞表面标记物； 具体来说，主要组织相容性复合物的表达 (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 进行分析，确定效果目标， 病毒基因中具有重要功能的区域将是 确定。 淋巴细胞和单核细胞的活性 将比较病毒的干扰能力 肺泡巨噬细胞生理学。 这些研究将提供见解 深入了解严重免疫缺陷的机制 艾滋病发病机制的核心。

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.