ROLE OF INFLAMMATION IN PULMONARY INJURY

炎症在肺损伤中的作用

• 批准号: 7415122
• 负责人: Borna Mehrad
• 金额: $ 161.07万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-16 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7415122
• 关键词: ROLE; INFLAMMATION; PULMONARY; INJURY

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.

描述(由申请人提供)： “炎症在肺损伤中的作用”旨在更好地了解导致肺的病理性炎症和随后的心肌功能障碍的分子和细胞机制。免疫细胞的疏通是炎症过程的中心，在全身和肺微循环中似乎受到不同的调节。林登的项目“肺中腺苷的分子和细胞靶点”专注于确定细胞因子和A2AAR(A2AAR)如何调节白细胞和内皮细胞(EC)，以及腺苷如何抑制博莱霉素诱导的肺部炎症。该项目和PPG负责人Joel Linden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炎症细胞中删除。Duling的项目“中性粒细胞向正常和炎症肺的运输”将识别黏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雾化、气管内或全身内脂多糖引起的白细胞向肺的运输。肺部对脂多糖的反应专家C.Ed Rose博士将协助Klaus Ley，他是调节白细胞黏附和渗出的主要权威。法国项目“肺损伤的心肺反应”将研究原位肺IRI降低心脏功能的机制。利用磁共振成像非侵入性测量心肌局部室壁运动的专家布伦特·弗伦奇将与磁共振波谱专家尤尔根·施拉德合作，评估心肌能量学。PPG得到了最先进的核心设施的支持：小鼠遗传学、炎性细胞贩运以及mRNA和蛋白质的量化。该计划被很好地整合，集中在肺部炎症和腺苷保护肺的机制的共同主题上。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，并可能催生新的治疗方法。

项目成果

Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability.

• DOI: 10.1016/j.it.2009.07.012
• 发表时间: 2009-11
• 期刊: Trends in immunology
• 影响因子: 16.8
• 作者: DiStasi MR;Ley K
• 通讯作者: Ley K

PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling.

• DOI: 10.1084/jem.20072660
• 发表时间: 2008-09-29
• 期刊: The Journal of experimental medicine
• 作者: Zarbock A;Abram CL;Hundt M;Altman A;Lowell CA;Ley K
• 通讯作者: Ley K

Adenosine A2A receptor activation on CD4+ T lymphocytes and neutrophils attenuates lung ischemia-reperfusion injury.

• DOI: 10.1016/j.jtcvs.2009.08.033
• 发表时间: 2010-02
• 期刊: JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
• 影响因子: 6
• 作者: Sharma, Ashish K.;Laubach, Victor E.;Ramos, Susan I.;Zhao, Yunge;Stukenborg, George;Linden, Joel;Kron, Irving L.;Yang, Zequan
• 通讯作者: Yang, Zequan

CD4+ T lymphocytes mediate acute pulmonary ischemia-reperfusion injury.

• DOI: 10.1016/j.jtcvs.2008.10.044
• 发表时间: 2009-03
• 期刊: JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
• 影响因子: 6
• 作者: Yang, Zequan;Sharma, Ashish K.;Linden, Joel;Kron, Irving L.;Laubach, Victor E.
• 通讯作者: Laubach, Victor E.

Phosphoinositide 3-kinase gamma required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung.

• DOI: 10.1183/09031936.00085509
• 发表时间: 2010-05
• 期刊: The European respiratory journal
• 作者: Reutershan J;Saprito MS;Wu D;Rückle T;Ley K
• 通讯作者: Ley K