Shared Mechanisms of Pulmonary Lymphocyte Activation by Bacteria and Toxicants
细菌和毒物激活肺淋巴细胞的共同机制
基本信息
- 批准号:7163144
- 负责人:
- 金额:$ 50.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-09-01 至 2011-08-31
- 项目状态:已结题
- 来源:
- 关键词:Pseudomonas aeruginosaacroleinair pollutionbacteriabiological signal transductioncell cell interactionchronic obstructive pulmonary diseasecytotoxic T lymphocyteenvironmental exposuregenetic modelsgenetically modified animalshazardous substanceshost organism interactionimmunologic receptorsimmunopathologylaboratory mouseleukocyte activation /transformationlung alveoluslymphocytemodel design /developmentnatural killer cellspathologic processphysiologic stressorreceptor expressionrespiratory epitheliumrespiratory infections
项目摘要
DESCRIPTION (provided by applicant):
Environmental exposure to fundamentally diverse agonists such as bacteria and air pollutants can signal through shared mechanisms to activate the innate immune system. Although the roles of pulmonary lymphocytes in response to bacterial infection are well established, the roles of pulmonary lymphocytes in response to air pollutants are unclear. We propose to explore the paradigm that the same lymphocyte effector functions necessary to protect the lung from pathogens can lead to chronic pulmonary disease when stimulated by persistent exposure to environmental toxicants. To understand shared roles and mechanisms of lymphocyte activation following bacterial infection and toxicant exposure, we will study epithelial cell lymphocyte interactions in response to the common bacteria Pseudomonas aeruginosa (PA) and the ubiquitous air pollutant, acrolein. PA is a well-characterized gram-negative bacterium that constitutes a major cause of nosocomial infections. Acrolein is a hazardous air pollutant found in tobacco smoke, photochemical smog and diesel exhaust. We have examined specific mediators involved in the signaling of epithelial cell stress to the pulmonary immune system and identified NKG2D receptor activation as a potential mechanistic link between epithelial cell stress and lymphocyte activation. The central hypothesis of this application is that chronic acrolein exposure induces NKG2D ligand expression on pulmonary epithelial cells, activates cytotoxic lymphocytes that contribute to the development of Chronic Obstructive Pulmonary Disease (COPD). The Specific Aims are to (i) determine the role of NKG2D receptor activation in the clearance of pulmonary PA infection, (ii) determine the role of NKG2D receptor activation in the development of acrolein-induced airspace enlargement, and (iii) define the consequences of conditional NKG2D ligand expression on pulmonary epithelial cells. These shared mechanisms represent potential disease points that may shift the immune response from protective to pathological. Further, the development of the novel conditional NKG2D ligand-expressing transgenic mouse model will allow us to dissect the mechanisms of epithelial cell-lymphocyte interactions in emphysema. The successful completion of these studies will provide a better understanding of the pathways and mechanisms of immune system activation in response to environmental exposures that contribute to the pathophysiology of chronic airway diseases.
描述(由申请人提供):
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 }}
Michael Borchers其他文献
Michael Borchers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('Michael Borchers', 18)}}的其他基金
Molecular and Cellular Pathogenesis of Pulmonary Langerhans Cell Histiocytosis
肺朗格汉斯细胞组织细胞增多症的分子和细胞发病机制
- 批准号:
10658208 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Natural Killer Cell Subpopulations in COPD Exacerbations
COPD 恶化中的自然杀伤细胞亚群
- 批准号:
10316151 - 财政年份:2020
- 资助金额:
$ 50.45万 - 项目类别:
Natural Killer Cell Subpopulations in COPD Exacerbations
COPD 恶化中的自然杀伤细胞亚群
- 批准号:
10578653 - 财政年份:2020
- 资助金额:
$ 50.45万 - 项目类别:
Natural Killer Cell Subpopulations in COPD Exacerbations
COPD 恶化中的自然杀伤细胞亚群
- 批准号:
10012049 - 财政年份:2020
- 资助金额:
$ 50.45万 - 项目类别:
Natural Killer Cell Functions in Lymphangioleiomyomatosis
自然杀伤细胞在淋巴管平滑肌瘤病中的功能
- 批准号:
10323021 - 财政年份:2019
- 资助金额:
$ 50.45万 - 项目类别:
Clec5a regulation of Macrophage function in COPD
Clec5a 对 COPD 巨噬细胞功能的调节
- 批准号:
8696486 - 财政年份:2014
- 资助金额:
$ 50.45万 - 项目类别:
Clec5a regulation of Macrophage function in COPD
Clec5a 对 COPD 巨噬细胞功能的调节
- 批准号:
9040253 - 财政年份:2014
- 资助金额:
$ 50.45万 - 项目类别:
Clec5a regulation of Macrophage function in COPD
Clec5a 对 COPD 巨噬细胞功能的调节
- 批准号:
9247243 - 财政年份:2014
- 资助金额:
$ 50.45万 - 项目类别:
Novel Reagents in Mouse Models of Autoimmune COPD
自身免疫性慢性阻塞性肺病小鼠模型中的新型试剂
- 批准号:
8166497 - 财政年份:2011
- 资助金额:
$ 50.45万 - 项目类别:
Novel Reagents in Mouse Models of Autoimmune COPD
自身免疫性慢性阻塞性肺病小鼠模型中的新型试剂
- 批准号:
8313878 - 财政年份:2011
- 资助金额:
$ 50.45万 - 项目类别:
相似国自然基金
Acrolein调控耳蜗核神经元-胶质细胞网络参与感音神经性耳聋发病机制的研究
- 批准号:81570922
- 批准年份:2015
- 资助金额:65.0 万元
- 项目类别:面上项目
acrolein在脊髓损伤后慢性疼痛发生发展中的作用及机制研究
- 批准号:81171052
- 批准年份:2011
- 资助金额:60.0 万元
- 项目类别:面上项目
相似海外基金
Early life bladder inflammatory events in female mice lead to subsequent LUTS in adulthood
雌性小鼠生命早期的膀胱炎症事件导致成年后的 LUTS
- 批准号:
10638866 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Core 3 - Biomarkers and Product Evaluation
核心 3 - 生物标志物和产品评估
- 批准号:
10628258 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
In vivo anti cancer natural product synthesis based on reaction with endogenous acrolein
基于与内源性丙烯醛反应的体内抗癌天然产物合成
- 批准号:
23KJ0944 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Prodrug Strategy by Diels-Alder Reaction with Cancer-Derived Acrolein
通过与癌症衍生的丙烯醛进行第尔斯-阿尔德反应的前药策略
- 批准号:
23K17971 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Receptor-mediated dysfunction of satellite glia and uninjured sensory neurons as a novel link between referred neuropathic pain and bladder disease
卫星胶质细胞和未损伤感觉神经元受体介导的功能障碍是牵涉性神经性疼痛和膀胱疾病之间的新联系
- 批准号:
10602919 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells
致癌烟草特异性亚硝胺诱导人类口腔细胞 DNA 中的无嘌呤/无嘧啶位点
- 批准号:
10856299 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Project 2 - Impact of Adolescent Vaping on Brain Health
项目 2 - 青少年电子烟对大脑健康的影响
- 批准号:
10628252 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Impact of Landfill Mitigation Efforts to Reduce Air Toxics in Bristol, Tennessee and Virginia
布里斯托尔、田纳西州和弗吉尼亚州垃圾填埋场缓解措施对减少空气有毒物质的影响
- 批准号:
10693558 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Project 2: Oxidative Stress and Harmful Constituent Levels Associated with Little Cigars
项目 2:与小雪茄相关的氧化应激和有害成分水平
- 批准号:
10665897 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别:
Pathophysiological Mechanisms of Chemical-Induced Acute Lung Injury
化学引起的急性肺损伤的病理生理机制
- 批准号:
10708438 - 财政年份:2023
- 资助金额:
$ 50.45万 - 项目类别: