Mechanisms of Eosinophil Effector Functions in the Lung

肺中嗜酸性粒细胞效应功能的机制

• 批准号: 7632048
• 负责人: JAMES Joseph LEE
• 金额: $ 12.1万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7632048
• 关键词: Achievement; Agonist; Allergens; Allergic; Antibodies; Asthma; Biological Models; Biology; Biomedical Research; Clinic; Cytoplasmic Granules; Development; Development Plans; Diphtheria Toxin; Doctor of Philosophy; Educational Activities; Foundations; Gene Transfer; Genes; Goals; Graduate Education; Human; Inflammation; Interleukin-5; Knockout Mice; Laboratories; Laboratory Research; Lung; Lung diseases; Mediating; Modeling; Molecular Biology; Mus; Pathology; Patients; Physiology; Proteins; Pulmonary Pathology; Reagent; Recruitment Activity; Research; Role; Small inducible cytokine A24; Technology; Training; Transgenic Model; Transgenic Organisms; Universities; Work; base; career; career development; chemokine; eosinophil; expectation; experience; human disease; novel; programs; success

The use of gene transfer technologies and the mouse as a model of human respiratory diseases aptlysummarizes the research program of the candidate, James (Jamie) J-.ee, Ph.D. This work forms the basis of the candidate's immediate career goals of expanding the breadth of his laboratory to includeincreasinglycomplex assessmentsof physiologically relevant endpoints of pathology. The achievement of these immediate goals, in turn, support the long term goals, including (i) To move the orientation of the lab from a molecular biology perspective to a physiology-based program and (ii)To expand the educational activities in mouse research within the Mayo Foundation, and Mayo ClinicArizona in particular,and to includethe regional graduate program at ArizonaState Uni versity. The institutional support and commitmentto research and graduate education offered byMayo Clinic, together with the expanding local university graduate programs in biomedical research, represent unique opportunities to create a collaborative center of focused efforts using the mouse as a model system of human disease research. A critical objective of this career development plan is to recruit and train motivatedstudents and fellows, capitalizing on the success of the laboratory's research activities.The goals of the researchproposal are to define the role(s) of eosinophils and eosinophil effector functions mediating allergic inflammation and, therefore, their roles in the development of pulmonary pathologies. The proposal exploits unique eosinophil- specific reagents and novel transgenic and gene knockout mice we have created in our studies ofeosinophil biology. The objectives will be achieved through the completion of the following aims: (1) To determine unequivocally the contribution(s)of eosinophils to the pulmonarypathologies arising in a transgenic model of asthma generated by the co-expression of JJL-5 and eotaxin-2; (2) To define mechanisms of eosinophil effector functions responsible for the pulmonarypathologiesoccurring in the IL-5/eotaxin-2 transgenicmodel of asthma; (3) To determine if degranulation and the release of granule proteins represents a mechanism by which eosinophils contribute to the pathologies arising in the IL-5/eotaxin-2 transgenic model of asthma.

使用基因转移技术和小鼠作为人类呼吸道疾病的模型适当地进行了 候选人詹姆斯（Jamie）J-.EE博士的研究计划这项工作构成了候选人的基础 扩大实验室广度以包括刺激性评估的直接职业目标 病理学与生理相关的终点。实现这些直接目标，反过来支持 长期目标，包括（i）将实验室的方向从分子生物学角度移动到 基于生理学的计划和（ii）扩展梅奥鼠标研究中的教育活动 尤其是基金会，尤其是梅奥诊所，包括亚利桑那州的地区研究生计划 大学。对研究和研究生教育的机构支持和承诺提供了Mayo诊所， 以及不断扩大的生物医学研究的当地大学研究生课程，代表了独特的 使用鼠标作为人类模型系统建立共同努力的协作中心的机会 疾病研究。该职业发展计划的一个关键目标是招募和培训激励人士 和研究员，利用实验室研究活动的成功。 定义嗜酸性粒细胞和嗜酸性粒细胞效应子功能的作用，介导过敏性炎症，并 因此，它们在肺部病理发展中的作用。该提案利用了独特的嗜酸性粒细胞 我们在嗜酸性粒细胞研究中创建的特定试剂以及新型的转基因和基因敲除小鼠 生物学。这些目标将通过完成以下目的实现：（1）确定 明确地，嗜酸性粒细胞对在转基因模型中产生的肺病理学的贡献 JJL-5和Eotaxin-2的共表达产生的哮喘； （2）定义嗜酸性粒细胞效应子的机制 负责哮喘的IL-5/eotaxin-2转基因模型中肺病理学的功能； （3）确定脱粒和颗粒蛋白的释放是否代表一种机制 嗜酸性粒细胞有助于哮喘的IL-5/eotaxin-2转基因模型引起的病理。