Lung Damage from P. carinii: pathogenesis and prevention

卡氏疟原虫肺损伤：发病机制和预防

• 批准号: 6668561
• 负责人: Francis Gigliotti
• 金额: $ 144.38万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668561
• 关键词: Pneumocystis carinii; Pneumocystis pneumonia; inflammation; lung injury

DESCRIPTION (provided by applicant): Pneumocystis carinii pneumonia (PcP) is a significant cause of morbidity and mortality in patients with a compromised immune system such as those with AIDS or those receiving immunosuppressive therapy for malignancy, organ transplantation or other underlying medical conditions. The central hypothesis for this proposed program project grant (PPG) is: lung injury during PcP is largely the result of the immune-mediated inflammatory response to P. carinii and that specific and effective control of this response will improve the morbidity and mortality associated with PcP. To test our hypothesis in mouse models of PcP we have set the following goals for this proposed PPG: 1) To elucidate the mechanisms by which lymphocytes, phagocytic cells and relevant soluble mediators interact to damage alveolar epithelial cells, perturb the surfactant system and interfere with normal lung function. 2) to utilize the knowledge gained through the completion of goal 1 to identify and test potential new adjunctive therapies for PcP based on control of specific injurious inflammatory pathways. To accomplish our goals we have assembled a multi-disciplinary group of investigators who bring expertise in microbiology, immunology, molecular biology, surfactant biochemistry and biophysics and respiratory cell and molecular biology to this project. This group of investigators will be able to examine the pathogenesis of PcP from the initial interaction between P. carinii and specific cells of the immune system through the development of a P. carinii-specific immune response then on to the effects of alveolar epithelial cells and surfactant with resultant end stage pulmonary dysfunction. This investigative effort will identify potential sites for therapeutic intervention to reduce the morbidity and mortality associated with PcP. I

描述（由申请人提供）： 卡氏肺囊虫肺炎 (PcP) 是导致免疫系统受损的患者发病和死亡的一个重要原因，例如艾滋病患者或因恶性肿瘤、器官移植或其他潜在疾病而接受免疫抑制治疗的患者。 该拟议计划项目拨款 (PPG) 的中心假设是：PcP 期间的肺损伤主要是对卡氏疟原虫免疫介导的炎症反应的结果，并且对这种反应的特异性和有效控制将改善与以下疾病相关的发病率和死亡率：五氯苯酚。 为了在 PcP 小鼠模型中检验我们的假设，我们为拟议的 PPG 设定了以下目标： 1）阐明淋巴细胞、吞噬细胞和相关可溶性介质相互作用损伤肺泡上皮细胞、扰乱表面活性剂系统并干扰正常肺功能的机制。 2) 利用通过完成目标 1 获得的知识，基于对特定有害炎症途径的控制来识别和测试潜在的新 PcP 辅助疗法。 为了实现我们的目标，我们组建了一个多学科研究小组，他们为该项目带来了微生物学、免疫学、分子生物学、表面活性剂生物化学和生物物理学以及呼吸细胞和分子生物学方面的专业知识。 这组研究人员将能够从卡氏疟原虫与免疫系统特定细胞之间的最初相互作用，到卡氏疟原虫特异性免疫反应的发展，然后再到肺泡上皮细胞和免疫系统的影响，来检查 PcP 的发病机制。表面活性剂导致终末期肺功能障碍。 这项调查工作将确定治疗干预的潜在地点，以降低与 PcP 相关的发病率和死亡率。 我