MACROPHAGE RECOGNITION AND PHAGOCYTOSIS OF RHODOCOCCUS

红球菌的巨噬细胞识别和吞噬作用

• 批准号: 3085403
• 负责人: MARY HONDALUS
• 金额: $ 8.23万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085403
• 关键词: Actinomycetales; Corynebacterium; alveolar macrophages; clone cells; complement receptor; disease /disorder model; fibroblasts; genetic strain; host organism interaction; laboratory mouse; leukocyte oxidative burst; lysosomes; macrophage; microorganism immunology; model design /development; monoclonal antibody; phagocytosis; radioimmunoassay; receptor binding

Rhodococcus equi is a facultative intracellular bacteria that produces pulmonary abscessation and pneumonia. Formerly thought only to be a veterinary pathogen, it is now recognized as an agent of disease in immunocompromised persons such as those undergoing immunosuppressive therapy and those with Acquired Immunodeficiency Syndrome (AIDS). In the lung, the organism is typically found within alveolar macrophages, and several groups have shown that it multiplies within macrophages in vitro. The goal of this research is to define hte mechanism of interaction between Rhodococcus equi and macrophages. We propose to perform initial studies using the murine model and then to concentrate on human and equine models. Studies of other intracellular organisms have found that the fate of an intracellular microbe can be altered by changing the receptor that is responsible for microbial entry. Therefore, we plan to study the macrophage receptors involved in rhodococcus recognition, the physiology and molecular biology of these receptors, and the alteration of these receptors following immunologic activation. We also plan to quantitate the binding and intracellular fate of R. equi in macrophages with specific deletions in one or more of their complement receptors. Specifically, we will: 1. Characterize the binding of Rhodococcus equi to macrophages. 2. Study the cellular biology of R. equi phagocytosis by macrophages. 3. Use molecular biological techniques to further analyze the phagocytosis of R. equi by macrophages. 4. Perform in vivo experiments to study the pathobiology of R. equi. The specific aims of this proposal provide a challenging opportunity for me to investigate the interaction of a microbial agent with its host cell. With the guidance of prominent researchers, I will develop the research skills and learn an assortment of techniques which can be applied not only to R. equi but also to a variety of other intracellular pathogens. In addition to the proposed research, the Ph.D. degree program in which I am enrolled, at Temple University School of Medicine, includes formal coursework, laboratory training and seminars. It is may intention to use this intensive training period to become an independent researcher in the basic sciences.

马红球菌是一种兼性胞内细菌， 肺水肿和肺炎。 以前只被认为是一个 兽医病原体，它现在被认为是一种病原体， 免疫功能不全的人，例如经历免疫抑制的人， 治疗和获得性免疫缺陷综合征（艾滋病）。 在 肺，该生物体通常在肺泡巨噬细胞内发现，并且 几个研究小组已经表明它在体外巨噬细胞内增殖。 本研究的目的是确定 马红球菌和巨噬细胞。 我们建议进行初步研究， 使用鼠模型，然后集中于人和马模型。 对其他细胞内生物的研究发现， 细胞内微生物可以通过改变受体来改变 负责微生物进入。 因此，我们计划研究 巨噬细胞受体参与红球菌识别，生理 以及这些受体的分子生物学， 免疫激活后的受体。 我们还计划量化 结合和细胞内命运的R.马在巨噬细胞中的特异性 一个或多个补体受体缺失。 我们特别 将： 1.表征马红球菌与巨噬细胞的结合。 2.研究了红毛菊的细胞生物学。巨噬细胞的等吞噬作用。 3.利用分子生物学技术进一步分析吞噬作用 钢筋混凝马巨噬细胞。 4.进行体内实验，研究R.等。 这项提案的具体目标为我提供了一个具有挑战性的机会 研究微生物制剂与其宿主细胞的相互作用。 在杰出研究人员的指导下，我将开展研究 技能和学习各种各样的技术，不仅可以应用 于r.马，但也对各种其他细胞内病原体。 除了这项研究之外，博士学位课程，其中我 我就读于天普大学医学院，包括正式的 课程、实验室培训和研讨会。 它可能打算使用 这一密集的培训期间，成为一个独立的研究人员， 基础科学