CONTROL OF TYPE II CELL FUNCTION BY PNEUMOCYSTIS CARINII

卡氏肺囊虫对 II 型细胞功能的控制

• 批准号: 2223104
• 负责人: WARD R RICE
• 金额: $ 21.25万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-04 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2223104
• 关键词: Pneumocystis carinii; Pneumocystis pneumonia; SDS polyacrylamide gel electrophoresis; cell type; cell wall; cellular pathology; disease /disorder model; enzyme linked immunosorbent assay; flow cytometry; immunosuppression; laboratory rat; lung alveolus; messenger RNA; monoclonal antibody; phosphatidylcholines; phospholipid inhibitor; phospholipids; protein kinase C; protozoal antigen; pulmonary surfactants; receptor binding; secretory protein; statistics /biometry; tissue /cell culture

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.

肺炎肺炎肺炎肺炎的明显肺功能障碍引起 在免疫功能低下的患者中。尽管有这个问题的幅度， 对肺囊藻的机制知之甚少 此肺功能障碍。拟议的研究将检验以下假设 肺囊藻carinii与肺泡II型细胞相互作用，该细胞合成 并分泌与表面活性剂相关的磷脂和蛋白质产生 肺炎肺炎肺炎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特定阶段 负责抑制II型的肺炎藻的成分 细胞功能。抑制成分的生化表征 将进行肺炎刺激的机制 影响磷脂和II型细胞的产生 将确定与表面活性剂相关的蛋白质。多克隆和 针对肺囊藻的成分的单克隆抗体 将用于定义与类型调节有关的特定表位 II细胞功能。这些体外研究将与 大鼠肺炎肺炎肺炎肺炎的体内模型，以确定 与孤立的II型细胞的体外观察是否与 完整的动物。这些研究的总体目的是确定 涉及肺功能障碍的细胞机制 肺炎刺激性肺炎。获得的数据将是无价的 为免疫功能低下的患者设计合理的治疗方法 伴有肺炎肺炎肺炎肺炎，将进一步了解我们对 通过肺泡II型细胞调节表面活性剂产生的因素。

项目成果

Synergistic combinations of Ro 11-8958 and other dihydrofolate reductase inhibitors with sulfamethoxazole and dapsone for therapy of experimental pneumocystosis.

Ro 11-8958 和其他二氢叶酸还原酶抑制剂与磺胺甲恶唑和氨苯砜的协同组合用于治疗实验性肺囊虫病。

• DOI: 10.1128/aac.37.7.1436
• 发表时间: 1993
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Walzer,PD;Foy,J;Steele,P;White,M
• 通讯作者: White,M

Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.

脒基腙治疗免疫抑制大鼠卡氏肺孢子虫肺炎。

• DOI: 10.1128/aac.38.11.2572
• 发表时间: 1994
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Walzer,PD;Foy,J;Runck,J;Steele,P;White,M;Klein,RS;Otter,BA;Sundberg,RJ
• 通讯作者: Sundberg,RJ

Fractionation of Pneumocystis carinii developmental stages by counterflow centrifugal elutriation and sequential filtrations.

通过逆流离心淘洗和顺序过滤对卡氏肺囊虫发育阶段进行分级。

• DOI: 10.1007/bf00932616
• 发表时间: 1994
• 期刊: Parasitology research
• 影响因子: 2
• 作者: DeStefano,JA;Foy,JM;Sullivan,DW;Dawes,SM;Cushion,MT;Babcock,GF;Sleight,RG;vanHalbeek,H;Walzer,PD
• 通讯作者: Walzer,PD