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 在免疫功能低下的患者身上。尽管这个问题很严重， 对卡氏肺孢子虫产生的机制知之甚少 这种肺功能障碍。这项拟议的研究将检验这一假设 卡氏肺孢子虫与肺泡II型细胞相互作用 并分泌表面活性物质相关的磷脂和蛋白质以产生 在卡氏肺孢子虫肺炎中观察到肺功能障碍。系统化 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型的成分 细胞功能。抑制性成分的生物化学表征 以及卡氏肺孢子虫的作用机制 影响II型细胞产生磷脂和 将测定与表面活性物质相关的蛋白质。多克隆和 针对卡氏肺孢子虫各组分的单抗 将被用来定义涉及类型调控的特定表位 II细胞功能。这些体外研究随后将与一种 卡氏肺孢子虫肺炎大鼠体内模型的建立 分离的II型细胞的体外观察是否与 完好无损的动物。这些研究的总体目标是确定 肺功能障碍产生的细胞机制 卡氏肺孢子虫肺炎。所获得的数据将是无价的 为免疫低下患者设计合理的治疗方法 卡氏肺孢子虫肺炎，并将进一步加深我们对 调节肺泡II型细胞产生表面活性物质的因素。

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.