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: 7072211
• 负责人: JAMES Joseph LEE
• 金额: $ 11.3万
• 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/7072211
• 关键词: Mechanisms; Eosinophil; Effector; Functions; Lung

DESCRIPTION (provided by applicant): The use of gene transfer technologies and the mouse as a model of human respiratory diseases aptly summarizes the research program of the candidate, James (Jamie) Lee, Ph.D. This work forms the basis of the candidate's immediate career goals of expanding the breadth of his laboratory to include increasingly complex assessments of 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 Clinic Arizona in particular, and to include the regional graduate program at Arizona State University. The institutional support and commitment to research and graduate education offered by Mayo 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 motivated students and fellows, capitalizing on the success of the laboratory's research activities. The goals of the research proposal 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 of eosinophil biology. The objectives will be achieved through the completion of the following aims: (1) To determine unequivocally the contribution(s) of eosinophils to the pulmonary pathologies 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 pulmonary pathologies occurring in the IL-5/eotaxin-2 transgenic model 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.

描述（由申请人提供）： 基因转移技术的使用以及小鼠作为人类呼吸道疾病模型的运用恰如其分地总结了候选人 James (Jamie) Lee 博士的研究计划。这项工作构成了候选人近期职业目标的基础，即扩大实验室的广度，以包括对病理学生理相关终点的日益复杂的评估。这些近期目标的实现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转向基于生理学的项目，以及（ii）扩大梅奥基金会（特别是亚利桑那州梅奥诊所）内小鼠研究的教育活动，并包括亚利桑那州立大学的地区研究生项目。梅奥诊所提供的机构支持和对研究和研究生教育的承诺，以及不断扩大的当地大学生物医学研究研究生项目，为创建一个使用小鼠作为人类疾病研究模型系统的集中工作协作中心提供了独特的机会。该职业发展计划的一个关键目标是利用实验室研究活动的成功来招募和培训有积极性的学生和研究员。该研究计划的目标是确定嗜酸性粒细胞和嗜酸性粒细胞效应器功能介导过敏性炎症的作用，以及它们在肺部病理发展中的作用。该提案利用了我们在嗜酸性粒细胞生物学研究中创建的独特的嗜酸性粒细胞特异性试剂以及新型转基因和基因敲除小鼠。这些目标将通过完成以下目标来实现： (1) 明确确定嗜酸性粒细胞对 JJL-5 和嗜酸细胞活化趋化因子 2 共表达产生的转基因哮喘模型中出现的肺部病理学的贡献； (2) 确定嗜酸性粒细胞效应功能与 IL-5/eotaxin-2 转基因哮喘模型中发生的肺部病理学相关的机制； (3) 确定脱颗粒和颗粒蛋白的释放是否代表嗜酸性粒细胞促成 IL-5/eotaxin-2 转基因哮喘模型中出现的病理的机制。