ROLE OF INFLAMMATION IN PULMONARY INJURY

描述（由申请人提供）： “炎症在肺损伤中的作用”旨在更好地理解负责肺部病理性炎症和随后的心肌功能障碍的分子和细胞机制。 免疫细胞的渗出是炎症过程的核心，并且似乎在全身和肺微循环中受到不同的调节。林登的项目“肺中腺苷的分子和细胞靶点”侧重于确定细胞因子和A2 A腺苷受体（A2 AAR）如何调节白细胞和内皮细胞（EC）以及腺苷如何抑制博来霉素诱导的肺部炎症。该项目和PPG的负责人Joel林登是腺苷受体和腺苷调节炎症和组织损伤方面的权威。A2AAR将被选择性地从靶向的炎症细胞中删除。 Duling的项目“正常和炎症肺的白细胞运输”将鉴定粘附分子和细胞因子及其受体，这些分子和细胞因子及其受体负责调节白细胞运输到由雾化、气管内或全身性LPS引起的炎症肺。C医生艾德罗斯是肺对内毒素反应的专家，他将协助克劳斯·莱伊，他是白细胞粘附和渗出调节的主要权威。 法国人的项目，“心脏对肺损伤的反应”将研究原位肺IRI降低心脏功能的机制。布伦特弗伦奇是一位使用磁共振成像非侵入性测量心肌局部室壁运动的专家，他将与磁共振波谱学权威于尔根？施拉德（Jurgen Schrader）合作评估心肌能量学。PPG由最先进的核心设施支持：小鼠遗传学，炎症细胞运输以及mRNA和蛋白质的定量。该计划是很好的整合，重点是肺部炎症和腺苷肺保护机制的共同主题。这些研究将为控制肺和心脏炎症和损伤的细胞和细胞因子提供新的见解，并可能产生新的治疗方法。

DESCRIPTION (provided by applicant): "Role of Inflammation in Pulmonary Injury" seeks to better understand molecular and cellular mechanisms responsible for pathological inflammation of the lung and consequent myocardial dysfunction. Diapedesis of immune cells is central to the inflammatory process and appears to be regulated differently in the systemic and pulmonary microcirculations. Project by Linden, "Molecular and Cellular Targets of Adenosine in Lung" focuses on identifying how cytokines and the A2A Adenosine receptor (A2AAR) regulate leukocytes and endothelial cells (EC) and how adenosine inhibits bleomycin-induced pulmonary inflammation. The project and PPG leader, Joel Linden, is an authority on adenosine receptors and adenosine regulation of inflammation and tissue injury. The A2AAR will be selectively deleted from targeted inflammatory cells. Project by Duling, "Neutrophil traffickinq to normal and inflamed lung" will identify adhesion molecules and cytokines and their receptors that are responsible for regulating leukocyte trafficking to the lung inflamed by aerosolized, intratracheal or systemic LPS. Dr. C. Ed Rose, an expert on the pulmonary response to LPS, will assist Klaus Ley, a leading authority on the regulation of the leukocyte adhesion and diapedesis. Project by French, "Cardiopulmonary Response to Lung Injury" will investigate the mechanisms by which in situ pulmonary IRI diminishes heart function. Brent French, an expert on the use of magnetic resonance imaging to non-invasively measure myocardial regional wall motion will collaborate with Jurgen Schrader, an authority in magnetic resonance spectroscopy to assess myocardial energetics. The PPG is supported by state-of-the art core facilities: mouse genetics, inflammatory cell trafficking, and quantification of mRNA and protein. The program is well integrated, focusing on common themes of pulmonary inflammation and mechanisms of lung protection by adenosine. These studies will provide new insights into the cells and cytokines that control lung and heart inflammation and injury and is likely to spawn new therapies.