SP-A MOUSE MODELS OF PNEUMOCYSTIS INFECTION

肺孢子虫感染的 SP-A 小鼠模型

• 批准号: 6638606
• 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/6638606
• 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)是一种低毒力的真菌，是引起 HIV患者肺炎(P)。表面活性蛋白(SP-A) 凝集素在寄主的先天免疫中起重要作用 肺部病原体。对SP-A与Pc相互作用的研究主要有 是在体外进行的，并产生了相互矛盾的结果。基因靶向 SP-A缺乏的小鼠比野生型小鼠更容易感染五氯苯酚 实施了同样的免疫抑制。该应用程序提出了 以下假设：SP-A促进Pc在脑内的清除 具有免疫活性的宿主；该活性可定位于 SP-A至少部分由肺泡巨噬细胞介导；SP-A延缓 发展并降低免疫受损宿主中PCP的严重程度； SP-A下调宿主对Pc的免疫/炎症反应。具体的 目的：1)分析SP-A对丙型肝炎病毒感染的影响。 具有免疫能力的宿主。这些研究将：1.1)调查 关于Pc从肺中清除的SP-A；1.2)确定 给予SP-A可逆转SP-A缺陷小鼠的变化 定位涉及的特定领域；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Pc对肺泡巨噬细胞的影响 SP-A对丙型肝炎病毒感染宿主免疫/炎症反应的影响2)分析 SP-A对免疫低下宿主PCP的影响这些研究将会： 2.1)分析SP-A在慢性前列腺炎发病中的作用 不同形式的免疫抑制；2.2)检测SP-A对 肺泡细胞、表面活性物质和肺功能的变化 与PCP一起发生；以及2.3)分析SP-A对主机的影响 在PCP康复期间发生的免疫/炎症反应。