SP-A MOUSE MODELS OF PNEUMOCYSTIS INFECTION

肺孢子虫感染的 SP-A 小鼠模型

• 批准号: 6390669
• 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/6390669
• 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.

卡氏肺孢子虫（Pc）是一种低毒力真菌， HIV感染者肺炎（P）。 表面活性剂蛋白（SP-A）， collectins，在宿主的天然免疫中起着重要的作用， 肺部病原体 关于SP-A与Pc相互作用的研究主要有 在体外进行，并产生了相互矛盾的结果。 基因靶向 SP-A缺陷小鼠似乎比野生型小鼠更容易受到PcP的影响 使用了相同的免疫抑制剂 申请书建议， 以下假设：SP-A促进Pc在 免疫活性宿主;这种活性可以定位于 SP-A至少部分由肺泡巨噬细胞介导; SP-A延迟了 发展和降低免疫功能低下的宿主中PcP的严重程度; SP-A下调宿主对Pc的免疫/炎症反应。 具体 目的：1）分析SP-A对Pc感染的影响， 免疫活性宿主。 这些研究将：1.1）调查 SP-A对Pc从肺中清除的影响; 1.2）确定 施用SP-A可以逆转SP-A缺陷小鼠的变化， 定位所涉及的特定结构域; 1.3）研究SP-A对 Pc与肺泡巨噬细胞的相互作用;以及1.4）分析 SP-A对宿主对Pc感染的免疫/炎症反应的影响。 2)分析 SP-A对免疫受损宿主中PcP的影响。 这些研究将： 2.1)分析SP-A对PcP形成的影响 不同形式的免疫抑制; 2.2）检查SP-A对 肺泡细胞、表面活性成分和肺功能的变化， 2.3）分析SP-A对宿主的影响 免疫/炎症反应发生在从PcP恢复期间。