MACROPHAGE RECONGNITION AND PHAGOCYTOSIS OF RHODOCOCCUS

红球菌的巨噬细胞识别和吞噬作用

• 批准号: 3085401
• 负责人: MARY HONDALUS
• 金额: $ 6.78万
• 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/3085401
• 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细胞内细菌，可产生 肺脓肿和肺炎。 以前以为只是一个 兽医病原体，现已被认为是动物疾病的媒介 免疫功能低下的人，例如正在接受免疫抑制的人 治疗和获得性免疫缺陷综合症（艾滋病）患者。 在 肺，该生物体通常存在于肺泡巨噬细胞内，并且 一些研究小组已经证明它可以在体外的巨噬细胞内增殖。 本研究的目标是定义之间相互作用的机制 马红球菌和巨噬细胞。 我们建议进行初步研究 使用小鼠模型，然后专注于人类和马模型。 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 负责微生物的进入。 因此，我们计划研究 巨噬细胞受体参与红球菌识别、生理学 这些受体的分子生物学，以及这些受体的改变 免疫激活后的受体。 我们还计划量化 马红线虫在巨噬细胞中的结合和细胞内命运 一种或多种补体受体的缺失。 具体来说，我们 将要： 1. 表征马红球菌与巨噬细胞的结合。 2. 研究马罗氏菌巨噬细胞吞噬作用的细胞生物学。 3.利用分子生物学技术进一步分析吞噬作用 巨噬细胞对 R.equip 的影响。 4. 进行体内实验以研究马河马的病理生物学。 该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 技能并学习各种技术，这些技术不仅可以应用 不仅针对马立克体，而且还针对多种其他细胞内病原体。 除了拟议的研究之外，博士学位。我参加的学位课程 我就读于坦普尔大学医学院，包括正式的 课程作业、实验室培训和研讨会。 可能有意使用 在这段强化训练期间成为一名独立研究员 基础科学。