PULMONARY SURFACTANT SYSTEM & RADIATION PNEUMONITIS

肺表面活性剂系统

• 批准号: 3167820
• 负责人: PHILIP RUBIN
• 金额: $ 24.69万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3167820
• 关键词: autoradiography; bleomycin; combination cancer therapy; cytotoxicity; histopathology; laboratory mouse; lung alveolus; lung disorder; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; pneumonia; pulmonary surfactants; radiation therapy dosage; radiobiology

The central concept of this research proposal is to develop sensitive and reproductible biochemical assays of radiation- induced lung damage in in vivo and in vitro models which are applicable to man, and to study the effects of radiation-induced alterations. The major focus of our investigations will shift to a search for biochemical markers of different target cells in addition to Type II alveolar pneumocytes and to find predictors for both later effects--pneumonitis and fibrosis. There are basic structural changes in type II pneumocytes and immediate biochemical alterations following radiation exposure of lung tissue that can lead to pneumonitis and have a potential to be utilized as diagnostic tools. In our three different murine models and a rabbit model, we found a slight dissociation of surfactant release, ususally at slightly lower doses, from lethality. The concept of quantification of pulmonary surfactant release by an apoprotein rather than a phospholipid will be coupled with newer techniques to measure and analyze for other proteins using two-dimensional gel electrophoresis and immunochemical analyses. Furthermore, a panel of monoclonal antibodies directed against surface antigens of the adult type II pneumocyte have been characterized and these will be constructed and utilized in examination of the lavage and, since some of these products do enter extracellular spaces and may gain access to the blood, serum samples. Preliminary studies have shown detection of the apoprotein antigen in the blood of exposed animals in direct proportion to the severity of the exposure. The expsure refers to non-radiation injury produced by nitrogen dioxide, oxygen, hyperoxia and oleic acid and will be repeated with radiation. A new direction of investigation will be to study the effects of radiation directly on the nucleus and genetic function of type II pneumocytes. An attempt will be made to correlate the cellular changes of type II cells with altered gene expression of surfactant synthesis. As a preliminary step to human studies following lung irradiation, serial lavaging in the clinic has been initiated to develop quantitative techniques to determine the alveolar surface being lavaged and a lung lavage profile of different biochemical factors that may act as predictors for either later pneumonitis or fibrosis.

这项研究的核心概念是发展 灵敏和可重复的辐射生化分析- 在体内和体外模型中诱导肺损伤， 适用于人类，并研究辐射引起的影响， 改变。 我们调查的重点将转移到 寻找不同靶细胞的生化标志物， 除了II型肺泡细胞， 造成了肺炎和纤维化 有基本 II型肺细胞的结构变化和即刻 肺组织放射性照射后的生化变化 这可能导致肺炎，并有可能被用作 诊断工具。 在我们的三种不同的小鼠模型和一种 在兔模型中，我们发现表面活性剂释放的轻微解离， 通常是在稍低的剂量下，从致死性。 的概念 通过载脂蛋白定量肺表面活性物质释放 而不是磷脂将与更新的技术相结合 用二维技术测量和分析其他蛋白质 凝胶电泳和免疫化学分析。 此外，委员会认为， 一组针对表面抗原的单克隆抗体 的成年II型肺细胞的特征， 这些将被建造和使用在检查 灌洗，由于这些产物中的一些确实进入细胞外， 空间，并可能获得血液，血清样本。 初步研究表明， 暴露动物血液中的抗原与 暴露的严重性。 expsure指的是无辐射 由二氧化氮、氧、高氧和油酸产生的损伤 酸，并将与辐射重复。 的新方向 调查将是研究辐射的影响直接对 II型肺细胞的细胞核和遗传功能。 一个 将尝试将II型细胞变化与 表面活性剂合成基因表达改变的细胞。 作为 肺部照射后人体研究的初步步骤， 临床上已经开始进行系列灌洗， 定量技术来确定肺泡表面 不同生化因子的灌洗和肺灌洗特征 这可能是以后肺炎或纤维化的预测因子。