MODULATION OF MONOCYTE AND ALVEOLAR MACROPHAGE ACTIVATION

该项目建议研究单核细胞和肺泡细胞的作用 巨噬细胞表面CD4在正常和疾病时炎性细胞功能中的作用 肺部。我们建议的研究的基础是基于观察到的 外周血单核细胞和肺泡巨噬细胞均表达 以及通过使用一种新型CD4通过CD4刺激这些细胞 最近克隆的结合性淋巴因子(淋巴细胞趋化因子，LCF) Center博士的实验室(项目1)导致了信号的激活 转导途径和基本细胞功能。简要总结一下， LCF与单核细胞CD4结合导致细胞内钙离子和IP3升高 伴随着增强的迁移和随后细胞表面的增加 MHC-II类抗原HLA-DR的表达以此为背景，我们 将通过以下方式研究单个核细胞CD4受体功能的选定方面 确定它所传递的信号以及由此产生的功能 它的激活。我们的实验有几个独特的部分。这个 首先是对来自同一来源的两种相关细胞类型的CD4的研究 允许我们询问有关这些过程的问题的个人 细胞黏附于内皮细胞，迁移到肺内， 体内和体内单核细胞转化为巨噬细胞的成熟过程 体外培养。其次，我们将能够研究CD4出现背后的原因 和在体外AM上的消失，并将这些变化与 单元的功能状态。最后，从法线派生的数据将是 应用于我们关于疾病个体中肉芽肿形成的知识 试图了解更多关于导致 肉芽肿性炎症，以及CD4细胞重新分布到 尤其是肺脏。

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.