Tissue-resident alveolar macrophages reduce O3-induced inflammation via MerTK mediated efferocytosis

Author:

Guttenberg M.A.ORCID,Vose A.T.ORCID,Birukova A.ORCID,Lewars K.,Cumming R.I.,Albright M.C.,Mark J.I.ORCID,Salazar C.J.,Swaminathan S.ORCID,Yu Z.,Sokolenko Yu. V.,Bunyan E.,Yaeger M.J.,Fessler M.B.ORCID,Que L.G.ORCID,Gowdy K.M.ORCID,Misharin A.V.ORCID,Tighe R.M.ORCID

Abstract

AbstractLung inflammation, caused by acute exposure to ozone (O3) – one of the six criteria air pollutants – is a significant source of morbidity in susceptible individuals. Alveolar macrophages (AMØs) are the most abundant immune cells in the normal lung and their number increases following O3exposure. However, the role of AMØs in promoting or limiting O3-induced lung inflammation has not been clearly defined. Here, we used a mouse model of acute O3exposure, lineage tracing, genetic knockouts, and data from O3-exposed human volunteers to define the role and ontogeny of AMØs during acute O3exposure. Lineage tracing experiments showed that 12, 24, and 72 h after exposure to O3(2 ppm) for 3h all AMØs were tissue-resident origin. Similarly, in humans exposed to FA and O3(200 ppb) for 135 minutes, we did not observe ∼21h post-exposure an increase in monocyte-derived AMØs by flow cytometry. Highlighting a role for tissue-resident AMØs, we demonstrate that depletion of tissue-resident AMØs with clodronate-loaded liposomes led to persistence of neutrophils in the alveolar space after O3exposure, suggesting that impaired neutrophil clearance (i.e., efferocytosis) leads to prolonged lung inflammation. Moreover, depletion of tissue-resident AMØ demonstrated reduced clearance of intratracheally instilled apoptotic Jurkat cells, consistent with reduced efferocytosis. Genetic ablation of MerTK – a key receptor involved in efferocytosis – also resulted in impaired clearance of apoptotic neutrophils followed O3exposure. Overall, these findings underscore the pivotal role of tissue-resident AMØs in resolving O3-induced inflammation via MerTK-mediated efferocytosis.

Publisher

Cold Spring Harbor Laboratory

Reference46 articles.

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Tissue-Resident Alveolar Macrophages Reduce Ozone-induced Inflammation via MerTK-mediated Efferocytosis;American Journal of Respiratory Cell and Molecular Biology;2024-06

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3