Inflammatory Cells and Lung Injury

炎症细胞和肺损伤

• 批准号: 7176216
• 负责人: Steven Lynn Kunkel
• 金额: $ 184.34万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7176216
• 关键词: Inflammatory; Cells; Lung; Injury

DESCRIPTION (provided by applicant): The strong inter-related research themes, common investigative interests, and collaborative ties of the scientists who comprise this renewal application have served as key underpins for over 20 years of continued research productivity under the auspices of this Program Project. The joint interactions of the scientific sections continue to promote a unified, hypothesis-driven objective of this application: To understand the mechanisms whereby various inflammatory mediators contribute to the initiation, maintenance, and resolution of acute and chronic lung inflammation and injury. This global objective will be addressed by the various sections using well establish experimental models to comprehend: 1) the role of C5a and C5a receptors, as they interact with specific cytokines and chemokines during acute lung injury (Project I, Peter A. Ward, M.D); 2) the mechanism of chemokine receptor (CCR4) and its ligands (TARC and MDC) in the initiation, maintenance, and progression/fibrosis of chronic granulomatous lung inflammation defined by specific cytokine phenotypes (project II, Steven L. Kunkel, Ph.D.); 3) to assess the mechanism(s) whereby FIZZ1 (Found in Inflammatory Zone 1), a novel protein induced by type 2 cytokines, participates in driving myofibroblasts to differentiate and participate in lung fibrosis (Project III, Sem H. Phan, M.D., Ph.D.); and 4) to determine the mechanistic role for a specific chemokine receptor (CCR6) and its ligand (MIP-3 alpha) in the development of dendritic and T-cell dependent, allergen-driven airway hyper-reactivity (Project IV, Nick Lukacs, Ph.D.). The scientific sections will be supported by an Administrative Core (Core A, Steven L. Kunkel, Ph.D.) and a Morphology Core (Core B, Kent J. Johnson, M.D) to aid in coordinating personnel and Financial matters and assist in the morphology and morphometric analyses, respectively. The overall rationale of this Program Project is to foster and focus the combined experience of investigators with established collaborative ties and proven expertise in specific areas of lung inflammation on the mechanistic contribution of C5a and its receptors, cytokines, chemokines, and growth and differentiation factors during the evolution of lung inflammation and injury. Data from the proposed experiments in this Program Project will provide novel insight into the mechanisms that dictate the pathology of acute and chronic lung inflammation and aid in developing strategies for new therapeutic targets.

描述（由申请人提供）： 在该计划项目的主持下，构成该续签应用程序的科学家的强烈相互关联研究主题，共同的研究兴趣和合作关系已成为20多年的持续研究生产力的关键基础。 科学部分的联合相互作用继续促进了该应用的统一，假设驱动的目标：了解各种炎症介体有助于急性和慢性肺部炎症和损伤的起始，维持和解决的机制。 各个部分将使用良好的实验模型来理解：1）C5A和C5A受体在急性肺损伤期间与特定细胞因子和趋化因子相互作用（Project I I，Peter A. Ward，M.D）； 2）趋化因子受体（CCR4）及其配体（TARC和MDC）的机制在慢性肉芽肿性肺炎症的起始，维持和进展/纤维化中的机制（由特定细胞因子表型定义的慢性肉芽肿性肺炎症（Project II，Steven L. Kunkel，Project） 3）评估FIZZ1（在炎症区1中发现）的机制（一种由2型细胞因子诱导的新型蛋白质）参与驱动肌纤维细胞以区分和参与肺纤维化（Project III，Sem H. Phan，M.D.，Projection III，Ph.D.，Ph.D。）； 4）确定特定趋化因子受体（CCR6）及其配体（MIP-3α）在树突状和T细胞依赖性，过敏蛋白驱动的气道高反应性（Project IV，Nick Lukacs，Ph.D。）中的机理作用。 科学部分将得到行政核心（Core A，Steven L. Kunkel，Ph.D.）和形态学核心（Core B，Kent J. Johnson，M.D）的支持，以协助协调人员和财务问题，并分别协助形态和形态计算分析。 该计划项目的总体原理是促进和集中研究人员的合并经验，并具有既定的协作关系，并在肺部炎症的特定领域进行了证明的专业知识，这些领域对C5A及其受体，细胞因子，趋化因子以及肺部炎症和损伤的过程中的机械贡献，细胞因子，趋化因子以及生长和分化因素的机理贡献。 该计划项目中提出的实验的数据将提供对决定急性和慢性肺部炎症病理学的机制的新见解，并有助于为新的治疗靶标制定策略。