Mediators and Mechanisms of Innate Immunity in the Lung

肺部先天免疫的介质和机制

• 批准号: 6442789
• 负责人: CRAIG GERARD
• 金额: $ 36.72万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6442789
• 关键词: JUN kinase; biological signal transduction; complement receptor; genetically modified animals; inflammation; laboratory mouse; lung disorder; mitogen activated protein kinase; molecular cloning; molecular pathology; receptor expression; respiratory hypersensitivity

DESCRIPTION (provided by applicant): In this proposal, we will explore a novel system of innate host defense in the cardiovascular and pulmonary systems. We and others have previously demonstrated a role for the complement anaphylatoxins C5a and C3a in the host defense in the lung. We now have identified a novel 7-transmembrane receptor that is a second C5a receptor. The mRNA for this receptor, besides being present on granulocytes, is most abundant in the heart and lung. While binding C5a with high affinity, the receptor in mouse and man bears a mutation in the region of the protein essential for coupling to G proteins. We will explore the hypothesis that this second C5a receptor mediates novel signaling properties independent of G proteins, and may serve as a regulator of the pro-inflammatory characterized C5a receptor. The characterization of this second C5a receptor may elucidate novel pathways for regulation of host defense and inflammation in the lung. Further, completion of these aims will allow further insight into mechanisms by which rational therapies for inflammatory lung disease may be approached.

描述（由申请人提供）： 在本提案中，我们将探索一种新颖的先天宿主防御系统 心血管和肺部系统。我们和其他人之前已经 证明了补体过敏毒素 C5a 和 C3a 在宿主中的作用 肺的防御。我们现在已经鉴定出一种新型的 7 次跨膜受体 这是第二个 C5a 受体。该受体的 mRNA 不仅是 存在于粒细胞上，在心脏和肺中含量最多。尽管 高亲和力结合C5a，小鼠和人的受体发生突变 位于与 G 蛋白偶联所必需的蛋白质区域。我们将 探索第二种 C5a 受体介导新信号传导的假设 特性独立于 G 蛋白，并且可以作为 G 蛋白的调节剂 促炎性 C5a 受体。 第二个 C5a 受体的表征可能阐明新的途径 用于调节宿主防御和肺部炎症。更远， 完成这些目标将有助于进一步了解机制 可以寻求针对炎症性肺部疾病的合理疗法。