SP-A MOUSE MODELS OF PNEUMOCYSTIS INFECTION

肺孢子虫感染的 SP-A 小鼠模型

• 批准号: 6537755
• 负责人: PETER D WALZER
• 金额: $ 38.25万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6537755
• 关键词: Pneumocystis carinii; Pneumocystis pneumonia; alveolar macrophages; disease /disorder model; gene targeting; genetically modified animals; immunity; laboratory mouse; pulmonary surfactants

Pneumocystis carinii (Pc) is a fungus of low virulence that is major cause of pneumonia (P) in HIV patients. Surfactant protein (SP-A), a member of the collectins, plays an important role in the host's innate immunity against pulmonary pathogens. Studies of the interaction of SP-A with Pc have mainly been conducted in vitro and have produced conflicting results. Gene targeted mice deficient in SP-A appear more susceptible to PcP than wild type mice administered the same immunosuppression. The application proposes the following hypotheses: SP-A facilitates the clearance of Pc in the immunocompetent host; this activity can be localized to specific domains of SP-A and is mediated at least in part by alveolar macrophages; SP-A delays the development and reduces the severity of PcP in the immunocompromised host; SP-A down regulates the host immune/inflammatory response to Pc. The specific aims are: 1) To analyze the effects of SP-A on Pc infection in the immunocompetent host. These studies will: 1.1) investigate the effects of SP-A on the clearance of Pc from the lungs; 1.2) determine if the administration of SP-A can reverse the changes in SP-A deficient mice and to localize the specific domains involved; 1.3) study the effects of SP-A on the interaction of Pc with alveolar macrophages; and 1.4) analyze the effects of SP-A on the host immune/inflammatory response to Pc infection. 2) To analyze the effects of SP-A on PcP in the immunocompromised host. These studies will: 2.1) analyze the effects of SP-A on the development of PcP induced by different forms of immunosuppression; 2.2) examine the influence of SP-A on the changes in alveolar cells, sufactant constituents, and lung function that occur with PcP; and 2.3) analyze the influence of SP-A on the host immune/inflammatory response that occurs during the recovery from PcP.

卡氏肺囊虫（Pc）是一种低毒力的真菌，是引起卡氏肺囊虫病的主要原因