{"doi":"10.1101/2023.11.06.565865","title":"Tissue-resident alveolar macrophages reduce O <sub>3</sub> -induced inflammation via MerTK mediated efferocytosis","abstract":"Abstract Lung inflammation, caused by acute exposure to ozone (O 3 ) – 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 O 3 exposure. However, the role of AMØs in promoting or limiting O 3 -induced lung inflammation has not been clearly defined. Here, we used a mouse model of acute O 3 exposure, lineage tracing, genetic knockouts, and data from O 3 -exposed human volunteers to define the role and ontogeny of AMØs during acute O 3 exposure. Lineage tracing experiments showed that 12, 24, and 72 h after exposure to O 3 (2 ppm) for 3h all AMØs were tissue-resident origin. Similarly, in humans exposed to FA and O 3 (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 O 3 exposure, 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 O 3 exposure. Overall, these findings underscore the pivotal role of tissue-resident AMØs in resolving O 3 -induced inflammation via MerTK-mediated efferocytosis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395333,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":772474,"name":"Aaron Vose","orcid":"0000-0003-2745-7070","position":1,"is_corresponding":false},{"id":479642,"name":"Anastasiya Birukova","orcid":"0000-0001-9168-138X","position":2,"is_corresponding":false},{"id":1170609,"name":"Kaitlyn Lewars","orcid":null,"position":3,"is_corresponding":false},{"id":1170210,"name":"R. Ian Cumming","orcid":"0000-0002-4218-6507","position":4,"is_corresponding":false},{"id":1090920,"name":"Michaela C. Albright","orcid":null,"position":5,"is_corresponding":false},{"id":648079,"name":"Jasper I. Mark","orcid":"0000-0002-6499-2198","position":6,"is_corresponding":false},{"id":1170610,"name":"Claudia J. Salazar","orcid":null,"position":7,"is_corresponding":false},{"id":553689,"name":"Suchitra Swaminathan","orcid":"0000-0002-8292-122X","position":8,"is_corresponding":false},{"id":1170211,"name":"Zhongxun Yu","orcid":"0000-0001-7297-9850","position":9,"is_corresponding":false},{"id":1170212,"name":"Yuliana V. Sokolenko","orcid":"0000-0001-9872-0484","position":10,"is_corresponding":false},{"id":1170213,"name":"Elsie G. Bunyan","orcid":"0009-0005-6589-6965","position":11,"is_corresponding":false},{"id":655293,"name":"Michael J. Yaeger","orcid":"0000-0001-7039-6360","position":12,"is_corresponding":false},{"id":270412,"name":"Michael B. Fessler","orcid":"0000-0002-8262-8613","position":13,"is_corresponding":false},{"id":572261,"name":"Loretta G. Que","orcid":"0000-0001-9188-9244","position":14,"is_corresponding":false},{"id":305236,"name":"Kymberly M. Gowdy","orcid":"0000-0002-7227-0697","position":15,"is_corresponding":false},{"id":1699,"name":"Alexander V. Misharin","orcid":"0000-0003-2879-3789","position":16,"is_corresponding":false},{"id":292273,"name":"Robert M. Tighe","orcid":"0000-0002-3465-9861","position":17,"is_corresponding":false},{"id":1072791,"name":"Marissa A. Guttenberg","orcid":"0000-0003-1737-8002","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:19:18.686170Z","pmid":"37986982","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}