MODULATION OF MONOCYTE AND ALVEOLAR MACROPHAGE ACTIVATION

单核细胞和肺泡巨噬细胞激活的调节

• 批准号: 3736927
• 负责人: JOHN BERNARDO
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3736927
• 关键词: CD4 molecule; Mycobacterium tuberculosis; T lymphocyte; acidity /alkalinity; alveolar macrophages; biological signal transduction; calcium flux; cell adhesion; cell differentiation; chemical kinetics; chemoattractants; cytokine receptors; enzyme inhibitors; flow cytometry; human tissue; inflammation; leukocyte activation /transformation; lung disorder; membrane potentials; monoclonal antibody; monocyte; peptides; phorbols; protein kinase C; tissue /cell culture

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.

该项目拟研究单核细胞和肺泡的作用 巨噬细胞表面 CD4 在正常和患病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均表达 表面 CD4，以及使用新型 CD4 通过 CD4 刺激这些细胞 最近克隆的结合淋巴因子（淋巴细胞趋化因子，LCF） 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。 简要总结一下， LCF 与单核细胞 CD4 结合导致细胞内 Ca++ 和 IP3 升高 伴随着迁移的增强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核细胞 CD4 受体功能的选定方面 确定其转导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 首先是 CD4 对来自同一细胞的两种相关细胞类型的研究 个人允许我们询问有关这些过程的问题 细胞粘附于内皮，迁移到肺中， 单核细胞在体内转化为巨噬细胞的成熟过程 体外。 其次，我们将能够研究CD4出现背后的原因 和体外 AM 上的消失，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了解 尝试更多地了解导致的基本细胞过程 一般性肉芽肿性炎症，以及 CD4 细胞重新分布到 尤其是肺。