SP-A MOUSE MODELS OF PNEUMOCYSTIS INFECTION

肺孢子虫感染的 SP-A 小鼠模型

• 批准号: 6077013
• 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/6077013
• 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.

肺炎藻藻（PC）是一种低毒力的真菌，是主要原因 HIV患者的肺炎（P）。 表面活性剂蛋白（SP-A），一个成员 collectins，在主持人的先天免疫力中起着重要作用 肺病原体。 SP-A与PC的相互作用的研究主要是 是在体外进行的，并产生了冲突的结果。 基因靶向 缺乏SP-A的小鼠比野生型小鼠更容易受到PCP的影响 给予相同的免疫抑制。 该申请提出了 以下假设：SP-A促进PC在 免疫能力的宿主；该活动可以定位于 SP-A，至少部分由肺泡巨噬细胞介导； SP-A延迟 开发和降低了免疫功能低下宿主中PCP的严重程度； SP-A向下调节对PC的宿主免疫/炎症反应。 具体 目的是：1）分析SP-A对PC感染的影响 免疫能力主机。 这些研究将：1.1）研究 SP-A从肺部清除PC上； 1.2）确定是否 SP-A的给药可以扭转SP-A缺乏小鼠的变化，并扭转 定位所涉及的特定域； 1.3）研究sp-a对 PC与肺泡巨噬细胞的相互作用； 1.4）分析 宿主对PC感染的免疫/炎症反应上的SP-A。 2）分析 SP-A对免疫功能低下宿主的PCP的影响。 这些研究将： 2.1）分析SP-A对诱导的PCP发展的影响 不同形式的免疫抑制； 2.2）检查SP-A对 肺泡细胞，舒张剂成分和肺功能的变化， PCP发生； 2.3）分析SP-A对宿主的影响 从PCP恢复期间发生的免疫/炎症反应。