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）： 使用基因转移技术和小鼠作为人类呼吸道疾病的模型，可以恰当地总结了候选人James（Jamie）Lee博士的研究计划。这项工作构成了候选人的直接职业目标基础，即扩大实验室的广度，包括对病理学上相关终点的日益复杂的评估。反过来，实现这些直接目标的实现支持了长期目标，包括（i）将实验室的取向从分子生物学的角度移动到基于生理学的计划，以及（ii）在Mayo基金会中扩大鼠标研究中的教育活动，以及Mayo Clinic Arizona的教育活动，尤其是在亚利桑那州立大学的区域研究生计划。 Mayo Clinic提供的机构支持和对研究和研究生教育的承诺以及生物医学研究的当地大学研究生课程，代表了创建使用Mouse作为人类疾病研究模型系统的集中精力协作中心的独特机会。该职业发展计划的一个关键目标是招募和培训积极进取的学生和研究员，利用实验室研究活动的成功。研究建议的目标是定义嗜酸性粒细胞和嗜酸性粒细胞效应子功能的作用，介导了过敏性炎症，因此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特异性试剂以及新型的转基因和基因敲除小鼠。目标将通过以下目的完成来实现：（1）明确确定嗜酸性粒细胞对由JJL-5和Eotaxin-2共表达产生的转基因哮喘模型中产生的嗜酸性病理学的贡献； （2）定义嗜酸性粒细胞效应子功能的机理，负责哮喘IL-5/eotaxin-2转基因模型中发生的肺病理； （3）确定脱粒化和颗粒蛋白的释放是否代表了一种机制，嗜酸性粒细胞有助于哮喘的IL-5/eotaxin-2转基因模型中产生的病理。