LUNG CELL METABOLISM IN VITRO

拟议中的研究的目标是确定分子 肺巨噬细胞产生的控制机制 促进吞噬细胞功能的衍生产品。上一首 研究表明，这是一种独特的构成和监管模式 几种补体蛋白在肺泡组织中的表达 巨噬细胞。该细胞在肺部宿主中的重要性 防御和炎症性肺病提供了理论基础 进行拟议的研究。初步数据与 相关cdna克隆的可用性表明了 建议进行的研究。转录、翻译和后翻译-- 补体蛋白(C_1、C_2、C_4、B因子、 C3)、补体受体(CR1、CR3)和调节蛋白 (C1抑制物，因子I)将在肺泡巨噬细胞中进行检测 在静息状态下和之后给药 内源性(细胞因子：IL-1、干扰素-γ)和外源性 (内毒素)介体。肺泡巨噬细胞亚群 将被研究并与其他单核吞噬细胞进行比较 使用单细胞和散装检测系统。功能和 免疫化学方法将被用来监测合成， Northern印迹分析用于检测稳态特异性mRNA 浓缩与核“径流”系统研究 抄写。拟议研究的长期目标是 肺巨噬细胞选择性调节剂的研究 功能，以限制炎症肺的组织损伤 没有引起寄主明显损害的疾病 对感染的防御。

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.