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T cell-mediated lung ischemia-reperfusion injury

T细胞介导的肺缺血再灌注损伤

基本信息

批准号：
8490408
负责人：
Victor E Laubach
金额：
$ 36.29万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8490408
关键词：
Ablation Acute Address Adoptive Transfer Alveolar Alveolar Macrophages Antibodies Antigens Blocking Antibodies Bone Marrow Bone Marrow Transplantation CD4 Positive T Lymphocytes Cells Chronic Clinical Research Coculture Techniques Complication Data Dendritic Cells Development Diphtheria Toxin Future Immune In Vitro Infiltration Inflammation Inflammatory Inflammatory Response Injury Interferons Interleukin-17 Interleukin-6 Ischemia Knock-out Knockout Mice Knowledge Laboratories Leukocytes Lung Lung Inflammation Lung Transplantation Macrophage Activation Measures Mediating Mediator of activation protein Mus NADPH Oxidase Neutrophil Infiltration Outcome Oxidative Stress Pathway interactions Phagocytes Postoperative Period Process Production Reactive Oxygen Species Reperfusion Injury Reperfusion Therapy Respiratory physiology Role Source T-Cell Activation T-Lymphocyte TNF gene Testing Transgenic Mice Transplant Recipients Transplantation Tumor Necrosis Factor-alpha Wild Type Mouse cytokine design human TNF protein improved in vivo in vivo Model interleukin-23 lung injury lung ischemia macrophage mortality neutrophil public health relevance small molecule

项目摘要

DESCRIPTION (provided by applicant): Ischemia-reperfusion (IR) injury remains a major source of early mortality after lung transplantation. The objective of this proposal is to better understand the cellular mechanisms that initiate and mediate this inflammatory process. Our laboratory has established that lung IR injury is dependent on alveolar macrophage activation, CD4+ T cell infiltration, and TNF-alpha induction. Recent data also supports an important role for IL-17 and IL-17-producing CD4+ T cells, such as iNKT, in mediating lung inflammation after IR. Thus Aim 1 will determine if iNKT cells initiate lung IR injury and neutrophil infiltration via IL-17 production. Oxidative stress and the release of reactive oxygen species via NADPH oxidase is also a component of IR injury as well as phagocytic cell activation. Thus Aim 2 will determine if NADPH oxidase-generated ROS is a key mechanism for the activation of iNKT cells after IR. Our overall hypothesis is that lung IR injury is initiated through CD4+ iNKT cell activation via production of IL-17 and NADPH oxidase-dependent ROS. Results from this proposal will help design successful strategies to improve outcomes in lung transplant recipients.

描述（由申请人提供）：缺血再灌注（IR）损伤仍然是肺移植术后早期死亡的主要原因。这一建议的目的是更好地了解细胞机制，启动和介导这一炎症过程。我们的实验室已经证实，肺IR损伤依赖于肺泡巨噬细胞活化、CD4+ T细胞浸润和tnf - α诱导。最近的数据也支持IL-17和产生IL-17的CD4+ T细胞（如iNKT）在IR后介导肺部炎症中的重要作用。因此，Aim 1将确定iNKT细胞是否通过IL-17的产生引发肺IR损伤和中性粒细胞浸润。氧化应激和通过NADPH氧化酶释放活性氧也是IR损伤和吞噬细胞活化的一个组成部分。因此，Aim 2将确定NADPH氧化酶产生的ROS是否是IR后iNKT细胞活化的关键机制。我们的总体假设是，肺IR损伤是通过产生IL-17和NADPH氧化酶依赖性ROS激活CD4+ iNKT细胞而引发的。这项建议的结果将有助于设计成功的策略来改善肺移植受者的预后。