Role of Splenic Pro-Resolving Mediators During Exposure to Particulate Air Pollution

暴露于颗粒空气污染期间脾促分解介质的作用

基本信息

  • 批准号:
    10658099
  • 负责人:
  • 金额:
    $ 56.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-05-01 至 2028-02-29
  • 项目状态:
    未结题

项目摘要

Exposure to ambient particulate matter (PM) is a risk factor for cardiovascular disease. Although the mechanisms by which PM induces pervasive multi-organ injury are still under investigation, evidence strongly implicates chronic inflammation as a primary driver of pathology. Whether exposure to fine PM (PM2.5) specifically impairs the endogenous pathways that promote the resolution of inflammation is not known. Therefore, the long-term goal of this project is to determine how exposure to PM impacts the resolution of inflammation and whether this contributes to PM exposure-exacerbated atherosclerosis. In work in progress, we discovered that in mice exposed to concentrated PM (PM2.5) for 30 days circulating erythrocytes expressed markers of premature aging and oxidative damage. In the spleens of these mice there was an expansion of the population of cells responsible for erythrocyte disposal, red pulp macrophages, while pathways related to erythrocyte turnover, heme metabolism, and iron cycling were upregulated. Additionally, we found that several factors related to hematopoiesis were induced in the tissue. These alterations were accompanied by a marked decrease in the abundance of specialized lipid mediators that promote resolution (SPMs) and their receptors. The changes in spleen are particularly critical because the spleen plays a central role in regulating immune response dynamics. It houses an important and distinct reservoir of monocytes, which can be rapidly mobilized and deployed in response to various insults. In addition to coordinating immune function, the spleen acts as a filter to remove senescent and damaged erythrocytes. Though patients survive following splenectomy, they are more likely to contract serious and life-threatening infections and have heightened risk of developing hematological malignancies and coronary artery disease among other disorders. Our preliminary studies suggest that exposure to PM2.5 may disrupt splenic homeostasis with targeted impacts on red pulp macrophages. As macrophages are the critical facilitators of erythrophagocytosis, maintenance of the splenic hematopoietic niche, and SPM actions, our central hypothesis is that PM2.5 exposure increases splenic macrophage erythrophagocytosis, which suppresses SPM production and permits local myelopoiesis, thereby enhancing monocyte egress and exacerbating vascular inflammation. To test this hypothesis, we will examine the effects of PM2.5 exposure on splenic macrophages, determine the impact of PM2.5 exposure on the splenic hematopoietic niche and delineate the contribution of splenic myelopoiesis to PM2.5-exacerbated atherosclerosis. This project will elucidate the effects of PM on the resolution of inflammation and will provide a new mechanism by which exposure to PM establishes a state of chronic, non-resolving inflammation that affects multiple organs and processes.
暴露于环境颗粒物(PM)是心血管疾病的一个危险因素。尽管这些机制

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 }}

Brian Edward Sansbury其他文献

Brian Edward Sansbury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 }}

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 56.64万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了