Lung Macrophage Programming in Acute Lung Injury

急性肺损伤中的肺巨噬细胞编程

基本信息

  • 批准号:
    10335239
  • 负责人:
  • 金额:
    $ 95.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-02-15 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Acute inflammatory lung diseases affect over 450 million people worldwide each year. Pathologic hallmarks include neutrophil accumulation, alveolar epithelial and endothelial cell injury, and loss of epithelial-capillary integrity. For alveolar repair to occur, inflammation must be halted, debris and inflammatory cells removed, injured tissue cells replaced, and capillary barrier function re-established. Macrophages are key players in all of these. The primary objective of this proposal is to create a Program in Lung Macrophage Biology that will determine how lung macrophages are programmed to halt inflammation and promote alveolar repair. A concept at the heart of the proposal is that of macrophage subsets. During health, the airspaces are occupied by a stable population of resident alveolar macrophages (RAM) that arise during embryogenesis and self-renew throughout life. RAMs remain during inflammation but are joined by recruited macrophages (RecM) that mature from circulating monocytes. These RecM remain in the lungs until alveolar function is restored, and then in most cases undergo apoptosis. However, in certain situations RecM escape apoptosis. We have shown that this is associated with the development of fibrosis. The precise roles played by RAMs vs RecM in the resolution of inflammation and promotion of tissue repair remain largely unknown. However, our data suggest that their respective roles are very different. In this context, the Program in Lung Macrophage Biology will explore 3 complementary themes. Theme 1 tests the hypothesis that RecM apoptosis is essential for the resolution of inflammation and that delayed apoptosis leads to fibrosis. The mechanisms that regulate the extrinsic apoptosis pathway and the intracellular proteins that block it will be studied. Theme 2 tests the hypothesis that binding of airway-derived mucins to Siglecs (a class of sialic acid-binding receptors with immunoinhibitory function) expressed on macrophages calibrates macrophage inflammatory responses. Theme 3 provides a tight link with the other themes and explores how cellular metabolism regulates macrophage inflammatory and pro-reparative functions and how it regulates survival of macrophage subsets. In this context, we propose that RecM preferentially use glycolysis as an energy source, whereas RAMs have increased utilization of the TCA cycle. HIF-1a is stabilized in RecM and is viewed as a central metabolic regulator. The 3 themes are further linked by their focus on differential functions of RAM vs RecM, the utilization of fresh human macrophages and shared use of cutting edge technologies. The Program leverages a multidisciplinary team of highly accomplished investigators, novel transgenic animal systems that we have developed, and a strong clinical research component. The latter includes whole human lungs obtained from donors that died with ARDS, bronchoscopy specimens from patients with ARDS, and LPS exposure studies with healthy human volunteers.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

William Janssen其他文献

William Janssen的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('William Janssen', 18)}}的其他基金

Aspen Lung Conference: Bridging the Gap between Innate and Adaptive Immunity in the Lung
阿斯彭肺部会议:弥合肺部先天免疫和适应性免疫之间的差距
  • 批准号:
    10469141
  • 财政年份:
    2022
  • 资助金额:
    $ 95.05万
  • 项目类别:
Lung Macrophage Programming in Acute Lung Injury
急性肺损伤中的肺巨噬细胞编程
  • 批准号:
    10225232
  • 财政年份:
    2018
  • 资助金额:
    $ 95.05万
  • 项目类别:
Lung Macrophage Programming in Acute Lung Injury
急性肺损伤中的肺巨噬细胞编程
  • 批准号:
    10553701
  • 财政年份:
    2018
  • 资助金额:
    $ 95.05万
  • 项目类别:
Lung Macrophage Programming in Acute Lung Injury
急性肺损伤中的肺巨噬细胞编程
  • 批准号:
    10094076
  • 财政年份:
    2018
  • 资助金额:
    $ 95.05万
  • 项目类别:
Macrophage Apoptosis in Resolution of Acute Lung Injury
巨噬细胞凋亡在缓解急性肺损伤中的作用
  • 批准号:
    8528053
  • 财政年份:
    2012
  • 资助金额:
    $ 95.05万
  • 项目类别:
Macrophage Apoptosis in Resolution of Acute Lung Injury
巨噬细胞凋亡在缓解急性肺损伤中的作用
  • 批准号:
    8460822
  • 财政年份:
    2012
  • 资助金额:
    $ 95.05万
  • 项目类别:
Hif-1 alpha metabolically reprograms recruited alveolar macrophages to promote lung repair
Hif-1 α 通过代谢重新编程招募的肺泡巨噬细胞以促进肺修复
  • 批准号:
    9309186
  • 财政年份:
    2012
  • 资助金额:
    $ 95.05万
  • 项目类别:
Macrophage Apoptosis in Resolution of Acute Lung Injury
巨噬细胞凋亡在缓解急性肺损伤中的作用
  • 批准号:
    8661268
  • 财政年份:
    2012
  • 资助金额:
    $ 95.05万
  • 项目类别:
Macrophage Apoptosis in Resolution of Acute Lung Injury
巨噬细胞凋亡在缓解急性肺损伤中的作用
  • 批准号:
    8297328
  • 财政年份:
    2012
  • 资助金额:
    $ 95.05万
  • 项目类别:
Macrophage Apoptosis in Resolution of Acute Lung Injury
巨噬细胞凋亡在缓解急性肺损伤中的作用
  • 批准号:
    8830993
  • 财政年份:
    2012
  • 资助金额:
    $ 95.05万
  • 项目类别:

相似海外基金

Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8429041
  • 财政年份:
    2011
  • 资助金额:
    $ 95.05万
  • 项目类别:
Analysis of extravascular lung water dynamics and exhaustive evaluation of pulmonary epithelial metabolites to establish a novel therapeutic approach for acute lung injury/ acute respiratory distress syndrome
分析血管外肺水动力学和详尽评估肺上皮代谢物,以建立急性肺损伤/急性呼吸窘迫综合征的新治疗方法
  • 批准号:
    22592023
  • 财政年份:
    2010
  • 资助金额:
    $ 95.05万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
OBSERVATIONAL STUDY OF ACUTE LUNG INJURY & ACUTE RESPIRATORY DISTRESS SYNDROME
急性肺损伤的观察性研究
  • 批准号:
    7603766
  • 财政年份:
    2007
  • 资助金额:
    $ 95.05万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8602427
  • 财政年份:
    2005
  • 资助金额:
    $ 95.05万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8602351
  • 财政年份:
    2005
  • 资助金额:
    $ 95.05万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8654999
  • 财政年份:
    2005
  • 资助金额:
    $ 95.05万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8844846
  • 财政年份:
    2005
  • 资助金额:
    $ 95.05万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8328484
  • 财政年份:
    2005
  • 资助金额:
    $ 95.05万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8328493
  • 财政年份:
    2005
  • 资助金额:
    $ 95.05万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8020428
  • 财政年份:
    2005
  • 资助金额:
    $ 95.05万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了