LUNG CELL METABOLISM IN VITRO

肺细胞体外代谢

• 批准号: 3353388
• 负责人: HARVEY R COLTEN
• 金额: $ 15.62万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3353388
• 关键词: actins; aerosols; alveolar macrophages; bactericidal immunity; cell adhesion; cell population study; complement; complement inhibitors; complement pathway; complement receptor; complementary DNA; densitometry; diagnostic respiratory lavage; endotoxins; exocytosis; gel electrophoresis; gene expression; genetic transcription; genetic translation; guinea pigs; immunochemistry; immunomodulators; inflammation; interferons; interleukin 1; laboratory mouse; lipopolysaccharides; lung; macrophage; messenger RNA; molecular cloning; monoclonal antibody; monocyte; nucleic acid probes; opsonin; oxygen tension; phagocytes; phagocytosis; phase change; plaque assay; pneumonia; properdin; protein biosynthesis; protein metabolism; radiotracer; scintillation spectrometry; single cell analysis; substance P; surface property; tissue /cell culture; tritium

The goal of the proposed studies is to determine the molecular mechanisms controlling production of pulmonary macrophage derived products that facilitate opsonophagocytosis. Previous studies suggest a unique pattern of constitutive and regulated expression of several complement proteins in the alveolar macrophage. The importance of this cell in pulmonary host defenses and inflammatory lung disease provides the rationale for the proposed studies. Preliminary data coupled with the availability of relevant cDNA clones indicate the feasibility of the proposed studies. The transcriptional, translational and post- synthetic control of complement proteins (C1, C2, C4, factor B, C3), complement receptors (Crl, Cr3) and regulatory proteins (C1 inhibitor, factor I) will be examined in alveolar macrophages under resting conditions and following administration of endogenous (cytokines: IL-1, IFN gamma) and exogenous (endotoxin) mediators. Sub-populations of alveolar macrophages will be studied and compared to other mononuclear phagocytes with single cell and bulk assay systems. Functional and immunochemical methods will be used to monitor synthesis, Northern blot analysis to measure steady state specific mRNA concentration and nuclear "run off" systems to study transcription. The long term objective of the proposed study is to define selective modulators of pulmonary macrophage function so as to limit tissue damage of inflammatory lung diseases without induction of a significant impairment of host defense against infection.

提出的研究的目的是确定分子 控制肺巨噬细胞产生的机制 衍生的促进脑吞噬作用的产品。 以前的 研究提出了一种独特的构成和调节模式 肺泡中几种补体蛋白的表达 巨噬细胞。 该细胞在肺宿主中的重要性 防御和炎症性肺部疾病提供了理由 对于拟议的研究。 初步数据与 相关cDNA克隆的可用性表明 提出的研究。 转录，翻译和后 - 补体蛋白质的合成控制（C1，C2，C4，因子B， C3），补体受体（CRL，CR3）和调节蛋白 （C1抑制剂，因子I）将在肺泡巨噬细胞中检查 在休息条件下以及执行后 内源性（细胞因子：IL-1，IFNγ）和外源性 （内毒素）介体。 肺泡巨噬细胞的亚种群 将研究并将其与其他单核吞噬细胞进行比较 带有单细胞和散装测定系统。 功能和 免疫化学方法将用于监测合成， 北印迹分析以测量稳态特异性mRNA 集中和核“逃跑”系统 转录。 拟议的研究的长期目标是 定义肺巨噬细胞的选择性调节剂 功能以限制炎症肺的组织损伤 疾病而无需诱导宿主的重大损害 防御感染。