PULMONARY SURFACTANT SYSTEM & RADIATION PNEUMONITIS

这项研究提案的中心概念是开发 灵敏和可重现的辐射生化分析- 在体内和体外模型中诱导的肺损伤 适用于人类，并研究辐射诱导的影响 改装。我们的调查重点将转移到 寻找不同靶细胞的生化标志物 添加到II型肺泡肺泡细胞和寻找预测因子 这两种后遗症--肺炎和纤维化。有基本的 II型肺泡细胞的结构变化和即刻 肺组织辐射暴露后的生化改变 这可能会导致肺炎，并有可能被用作 诊断工具。在我们的三个不同的小鼠模型和一个 兔模型，我们发现表面活性物质释放轻微解离， 通常剂量稍低，致命性较差。这一概念 载脂蛋白对肺表面活性物质释放的定量研究 而不是磷脂将与新的技术相结合 利用二维图像对其他蛋白质进行测量和分析 凝胶电泳和免疫化学分析。此外， 一组针对表面抗原的单抗 成人II型肺泡细胞的特征和 这些将被建造并用于检查 灌洗，因为其中一些产品确实进入了细胞外 空间，并可能获得血液，血清样本。 初步研究表明，已检测到载脂蛋白 暴露动物血液中的抗原与 暴露的严重程度。压力指的是无辐射 二氧化氮、氧气、高氧和油酸造成的伤害 酸，并将重复与辐射。一个新的方向 调查将直接研究辐射对人类健康的影响 II型肺泡细胞的核和遗传功能。一个 将尝试将II型的细胞变化关联起来 表面活性物质合成基因表达改变的细胞。作为一名 肺部照射后人体研究的初步步骤， 已开始在临床上开展系列洗涤 确定肺泡表面的定量技术 不同生化因素的灌洗及肺灌洗情况 这可以作为日后肺炎或纤维化的预测指标。

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.