CONTROL OF TYPE II CELL FUNCTION BY PNEUMOCYSTIS CARINII

卡氏肺孢子虫肺炎导致严重肺功能障碍 免疫功能低下的患者。尽管这个问题很严重， 关于卡氏肺孢子虫产生 肺功能障碍拟议的研究将检验以下假设： 卡氏肺孢子虫与肺泡II型细胞相互作用， 并分泌与表面活性剂相关的磷脂和蛋白质， 卡氏肺孢子虫肺炎中观察到的肺功能障碍。系统 将进行研究，以确定发展阶段和具体的 卡氏肺孢子虫抑制II型 细胞功能抑制成分的生化表征 以及卡氏肺孢子虫 影响II型细胞产生磷脂， 将测定表面活性剂相关蛋白。多克隆和 抗卡氏肺孢子虫组分的单克隆抗体 将被用来定义参与调节型 II细胞功能。然后将这些体外研究与 大鼠卡氏肺孢子虫肺炎的体内模型，以确定 分离的II型细胞的体外观察结果是否与 完整的动物。这些研究的总体目标是确定 肺功能障碍的细胞机制 卡氏肺孢子虫肺炎。获得的数据将是非常宝贵的， 为免疫功能低下的患者设计合理的治疗方法 卡氏肺孢子虫肺炎，并将进一步了解 调节肺泡II型细胞产生表面活性剂的因子。

Significant lung dysfunction results from Pneumocystis carinii pneumonia in immunocompromised patients. Despite the magnitude of this problem, little is known of the mechanisms by which Pneumocystis carinii produces this lung dysfunction. The proposed study will test the hypothesis that Pneumocystis carinii interacts with alveolar Type II cells which synthesize and secrete surfactant-associated phospholipids and proteins to produce the lung dysfunction observed in Pneumocystis carinii pneumonia. Systematic studies will be undertaken to identify developmental stages and specific components of Pneumocystis carinii responsible for inhibition of Type II cell function. A biochemical characterization of the inhibitory components will be undertaken and the mechanism by which Pneumocystis carinii influences Type II cell production of phospholipids and surfactant-associated proteins will be determined. Polyclonal and monoclonal antibodies directed against components of Pneumocystis carinii will be utilized to define specific epitopes involved in regulation of Type II cell function. These in vitro studies will then be correlated with an in vivo model of Pneumocystis carinii pneumonia in the rat, to determine whether in vitro observations with isolated Type II cells are relevant to the intact animal. The overall objective of these studies is to determine cellular mechanisms involved in production of lung dysfunction during Pneumocystis carinii pneumonia. The data obtained will be invaluable in designing rational therapeutic approaches for immunocompromised patients with Pneumocystis carinii pneumonia and will further our understanding of factors regulating surfactant production by the alveolar Type II cell.