Mechanisms of Eosinophil Effector Functions in the Lung

利用基因转移技术和小鼠作为人类呼吸道疾病的模型很容易总结 候选人James(Jamie)J-.ee博士的研究计划。这项工作构成了候选人 直接的职业目标是扩大他的实验室的广度，包括对 病理学的生理上相关的终点。这些眼前目标的实现反过来又支持 长期目标，包括(I)将实验室的方向从分子生物学角度转移到 以生理学为基础的方案和(Ii)在Mayo扩大老鼠研究方面的教育活动 基金会，特别是亚利桑那州的梅奥诊所，并包括亚利桑那州立大学的区域研究生课程 大学。梅奥诊所为研究和研究生教育提供的机构支持和承诺， 与不断扩大的本地大学生物医学研究研究生课程一起，代表着独特的 使用鼠标作为人类的模型系统来创建集中工作的协作中心的机会 疾病研究。这一职业发展计划的一个关键目标是招募和培训有动力的学生 和研究员，利用实验室研究活动的成功。研究提案的目标 是确定嗜酸性粒细胞和嗜酸性粒细胞效应器功能在调节变态反应性炎症中的作用(S)， 因此，它们在肺病理发展中的作用。这项提议利用了独特的嗜酸性粒细胞- 我们在嗜多染红细胞的研究中创造了特定的试剂和新型的转基因和基因敲除小鼠 生物学。目标将通过完成以下目标来实现：(1)确定 明确地说，嗜酸性粒细胞在转基因猪肺组织病理中的作用(S) JJL-5和嗜酸性粒细胞趋化因子-2共表达所致哮喘；(2)确定嗜酸性粒细胞效应分子的机制 哮喘IL-5/嗜酸性粒细胞趋化因子-2转基因模型中肺病理发生的功能； (3)确定颗粒蛋白质的脱粒和释放是否代表了一种 嗜酸性粒细胞参与了IL-5/eoaxin-2转基因哮喘模型的病理过程。

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.