Regulation of Ozone Induced Neutrophilic Lung Inflammation by ATP Synthase Complex V
ATP合酶复合物V对臭氧诱导的中性粒细胞性肺部炎症的调节
基本信息
- 批准号:RGPIN-2021-02784
- 负责人:
- 金额:$ 2.04万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2022
- 资助国家:加拿大
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Inflammation is a protective response against physical or chemical perturbation of the host environment. Ozone is a toxic environmental pollutant and is attributed to cause neutrophilic lung inflammation and injury. Although lungs are usually patrolled by resident neutrophils, a fulminant neutrophil response in the lungs is associated with disruption of the alveolar capillary barrier and impaired lung function. The fundamental mechanisms of neutrophil recruitment and their role in ozone-induced lung inflammation are not fully understood. Thus, the primary thrust of my research is to understand the fundamental mechanisms of neutrophil activation and their role in lung inflammation using an array of in vitro, intravital and in vivo cell and molecular methods. I have recently developed and characterized a sophisticated model of lung inflammation induced with low dose (0.05 ppm) ozone in C57BL/6NJ strain mice. This ozone-induced lung inflammation is characterized by marked neutrophil and eosinophil cell death, formation of nuclear extracellular traps (NETs), platelet clumping and reduced alveolar contraction. We made a novel observation of expression of the ß subunit of ATP synthase complex V (ATPS-V) in the lung vasculature and alveolar septa of ozone-exposed mice. But the fundamental role of ATPS-V in lung inflammation specifically neutrophil migration and alveolar permeability is not known. Considering that there is previous evidence of role of ATPS-V in neutrophil migration, my short term objectives are to use this model to address the following fundamental questions: 1. Does ATPS-V enhance ozone induced acute lung neutrophil migration and activation? 2. Does ATPS-V recover ozone induced alveolar contractile dynamics? 3. Does ATPS-V protect against ozone induced compromised alveolar barrier? I will use my expertise in the use of advanced methods such as microscopy enabled cell phenotyping, computed tomography (CT), synchrotron x-ray multiple image radiography (MIR), intravital lung imaging and micro positron emission tomography (PET-CT) to address these fundamental questions. The current grant proposes the utilization of cross-disciplinary natural sciences in order to reveal fundamental effects of ozone inhaled with the air. The data obtained from the proposed experiments will enhance our understanding of mechanisms of lung inflammation induced with low dose exposure to ozone. The findings will elaborate on the hitherto unknown role of ATPS-V in lung inflammation specifically neutrophil migration, alveolar capillary permeability and alveolar contractile function. The studies will further provide new imaging and in vivo tools to study organ physiology. The fundamental data may, at some point, influence environmental policies in Canada. Lastly, there is contribution to the HQP training using advanced and unique imaging tools at Canada's only Synchrotron facility.
炎症是针对宿主环境的物理或化学扰动的保护性反应。臭氧是一种有毒的环境污染物,可引起嗜肺性肺部炎症和损伤。虽然肺内通常有中性粒细胞巡逻,但肺内爆发性中性粒细胞反应与肺泡毛细血管屏障破坏和肺功能受损有关。中性粒细胞募集的基本机制及其在臭氧诱导的肺部炎症中的作用尚未完全了解。因此,我的研究的主要目的是了解中性粒细胞活化的基本机制及其在肺部炎症中的作用,使用一系列体外,活体和体内细胞和分子方法。我最近在C57 BL/6 NJ品系小鼠中开发了一种用低剂量(0.05 ppm)臭氧诱导的复杂肺部炎症模型并进行了表征。这种臭氧诱导的肺部炎症的特征在于显著的中性粒细胞和嗜酸性粒细胞死亡、细胞核细胞外陷阱(NET)的形成、血小板聚集和肺泡收缩减少。我们对臭氧暴露小鼠肺血管和肺泡隔中ATP合成酶复合物V(ATPS-V)的亚单位的表达进行了新的观察。但ATPS-V在肺部炎症中的基本作用,特别是中性粒细胞迁移和肺泡通透性尚不清楚。考虑到之前有证据表明ATPS-V在中性粒细胞迁移中的作用,我的短期目标是使用这个模型来解决以下基本问题:1。ATPS-V是否增强臭氧诱导的急性肺中性粒细胞迁移和活化? 2. ATPS-V能否恢复臭氧引起的肺泡收缩动力学?3. ATPS-V是否能防止臭氧引起的肺泡屏障受损?我将利用我的专业知识,在使用先进的方法,如显微镜启用细胞表型,计算机断层扫描(CT),同步加速器X射线多图像放射摄影(MIR),活体肺成像和微型正电子发射断层扫描(PET-CT),以解决这些基本问题。目前的赠款建议利用跨学科的自然科学,以揭示空气中吸入臭氧的基本影响。从拟议的实验中获得的数据将加强我们对低剂量臭氧暴露引起的肺部炎症机制的理解。这些发现将详细阐述ATPS-V在肺部炎症中迄今未知的作用,特别是中性粒细胞迁移,肺泡毛细血管通透性和肺泡收缩功能。这些研究将进一步提供新的成像和体内工具来研究器官生理学。这些基本数据可能会在某些时候影响加拿大的环境政策。最后,在加拿大唯一的同步加速器设施中使用先进和独特的成像工具为HQP培训做出了贡献。
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)
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Aulakh, Gurpreet其他文献
Adhesion Molecules in Lung Inflammation from Repeated Glyphosate Exposures.
- DOI:
10.3390/ijerph20085484 - 发表时间:
2023-04-12 - 期刊:
- 影响因子:0
- 作者:
Pandher, Upkardeep;Kirychuk, Shelley;Schneberger, David;Thompson, Brooke;Aulakh, Gurpreet;Sethi, R S;Singh, Baljit - 通讯作者:
Singh, Baljit
Aulakh, Gurpreet的其他文献
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{{ truncateString('Aulakh, Gurpreet', 18)}}的其他基金
Regulation of Ozone Induced Neutrophilic Lung Inflammation by ATP Synthase Complex V
ATP合酶复合物V对臭氧诱导的中性粒细胞性肺部炎症的调节
- 批准号:
RGPIN-2021-02784 - 财政年份:2021
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Regulation of Ozone Induced Neutrophilic Lung Inflammation by ATP Synthase Complex V
ATP合酶复合物V对臭氧诱导的中性粒细胞性肺部炎症的调节
- 批准号:
DGECR-2021-00132 - 财政年份:2021
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Launch Supplement
Microbial dynamics in sediments of recovering lakes: the influence of organic matter loading
恢复湖泊沉积物中的微生物动态:有机质负荷的影响
- 批准号:
462802-2014 - 财政年份:2014
- 资助金额:
$ 2.04万 - 项目类别:
University Undergraduate Student Research Awards
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