Mediators and Mechanisms of Innate Immunity in the Lung

描述（由申请人提供）： 在这个提议中，我们将探索一种新的先天宿主防御系统， 心血管和肺系统。我们和其他人以前 证明了补体过敏毒素C5 a和C3 a在宿主中的作用 肺的防御。我们现在已经确定了一种新的7-跨膜受体 这是第二种C5 a受体。这种受体的mRNA除了 存在于粒细胞上，在心脏和肺中最丰富。而 以高亲和力结合C5 a，小鼠和人的受体具有突变 在与G蛋白偶联所必需的蛋白质区域。我们将 探索第二种C5 a受体介导新信号传导的假设 性质独立的G蛋白，并可能作为一个调节器的 促炎特征的C5 a受体。 这第二个C5 a受体的特性可能阐明新的途径 调节宿主防御和肺部炎症。此外，本发明还 这些目标的完成将使人们能够进一步深入了解 炎症性肺病的合理治疗方法可能会被探讨。

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.