MODULATION OF MONOCYTE AND ALVEOLAR MACROPHAGE ACTIVATION

本项目拟探讨单核细胞和肺泡巨噬细胞的作用 巨噬细胞表面CD4在炎症细胞功能中的作用 肺 我们提出的研究的基础是基于观察结果 外周血单核细胞和肺泡巨噬细胞都表达 表面CD4，以及使用新CD4通过CD4刺激这些细胞 淋巴细胞趋化因子（LCF）是最近克隆的一种结合淋巴因子 由中心博士实验室（项目1）导致信号激活 转导途径和基本细胞功能。 简而言之， LCF与单核细胞CD4结合导致细胞内Ca ++和IP3升高 伴随着增强的迁移和随后的细胞表面增加 表达MHC II类抗原HLA-DR。以此为背景，我们 将研究单核细胞CD4受体功能的选定方面， 确定它所传递的信号和由其产生的功能， 其激活。 我们的实验有几个独特的部分。 的 首先是研究CD4对两种相关细胞类型的影响， 个人允许我们问问题的过程中，这些 细胞粘附于内皮细胞，迁移到肺内， 成熟过程中，单核细胞在体内转化为巨噬细胞， 体外 其次，我们将能够研究CD4出现背后的原因， 和消失，并将这些变化与 细胞的功能状态。 最后，从法线导出的数据将是 应用于我们对患病个体肉芽肿形成的认识， 试图了解更多的基本细胞过程， 肉芽肿性炎症，CD4细胞重新分布到 尤其是肺。

This project proposes to investigate the role of monocyte and alveolar macrophage surface CD4 in inflammatory cell function in normal and diseased lungs. The basis of our proposed studies is predicated on the observations that the peripheral blood monocyte and the alveolar macrophage both express surface CD4, and that stimulation of these cells via CD4 using a novel CD4 binding lymphokine (Lymphocyte Chemoattractant Factor, LCF) recently cloned by Dr. Center's laboratory (Project 1) results in activation of signal transduction pathways and essential cell functions. Briefly summarized, LCF binding to monocyte CD4 results in rises in intracellular Ca++ and IP3 accompanied by enhanced migration and subsequent increases in cell surface expression of the MHC Class II antigen HLA-DR. With this as background, we will study selected aspects of mononuclear cell CD4 receptor function by determining the signals it transduces and the functions that result from its activation. There are several unique parts of our experiments. The first is the study of CD4 on two related cell types from the same individuals permitting us to ask questions about the process by which these cells adhere to endothelium, migrate into lung, the events of the maturation process as the monocyte converts to macrophage in vivo and in vitro. Second, we will be able to study the causes behind CD4 appearance and disappearance on the AM in vitro, and relate these changes with functional state of the cell. Last, the data derived from normals will be applied to our knowledge of granuloma formation in diseased individuals in an attempt to learn more about the basic cellular processes that lead to granulomatous inflammation in general, and CD4 cell redistribution to the lung in particular.