{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T07:51:57Z","timestamp":1781596317936,"version":"3.54.5"},"reference-count":17,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000096","name":"National Center on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["U54 MD013368"],"award-info":[{"award-number":["U54 MD013368"]}],"id":[{"id":"10.13039\/100000096","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Lung exposures to dusts, pollutants, and other aerosol particulates are known to be associated with pulmonary diseases such as asthma and Chronic Obstructive Pulmonary Disease. These health impacts are attributed to the ability of aerosol components to induce pulmonary inflammation, which promotes tissue remodeling, including fibrosis, tissue degradation, and smooth muscle proliferation. Consequently, the distribution of these effects can have a significant impact on the physiologic function of the lung. In order to study the impact of distribution of inhaled particulates on lung pathogenesis, we compared the effect of different methods of particle delivery. By comparing intranasal versus aerosol delivery of fluorescent microspheres, we observed strikingly distinct patterns of particle deposition; intranasal delivery provided focused deposition concentrated on larger airways, while aerosol delivery showed unform deposition throughout the lung parenchyma. Recognizing that the impacts of inflammatory cells are contingent upon their recruitment and behavior, we postulate that these variations in distribution patterns can result in significant alterations in biological responses. To elucidate the relevance of these findings in terms of biological representation, we subsequently conducted an investigation into the responses elicited by the administration of endotoxin (bacterial Lipopolysaccharide, or LPS) in a transgenic neutrophil reporter mouse model. As with the microsphere results, patterns of recruited neutrophil inflammatory responses matched the delivery method; that is, despite the active migratory behavior of neutrophils, inflammatory histopathology patterns were either focused on large airways (intranasal administration) or diffusely throughout the parenchyma (aerosol). These results demonstrate the importance of modes of aerosol delivery as different patterns of inflammation and tissue remodeling will have distinct impacts on lung physiology.<\/jats:p>","DOI":"10.1371\/journal.pone.0289373","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T18:55:16Z","timestamp":1701111316000},"page":"e0289373","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Route of administration significantly affects particle deposition and cellular recruitment"],"prefix":"10.1371","volume":"18","author":[{"given":"Keziyah","family":"Yisrael","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan W.","family":"Drover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malia L.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Anguiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nala","family":"Kachour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Cocker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5962-9458","authenticated-orcid":true,"given":"David D.","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"issue":"1","key":"pone.0289373.ref001","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1089\/jam.2006.19.110","article-title":"Ciliary function and the role of cilia in clearance.","volume":"19","author":"W. Stannard","year":"2006","journal-title":"Journal of aerosol medicine: the official journal of the International Society for Aerosols in Medicine"},{"issue":"3","key":"pone.0289373.ref002","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/imm.13143","article-title":"Tissue-resident innate immunity in the lung","volume":"159","author":"A. Ardain","year":"2020","journal-title":"Immunology"},{"key":"pone.0289373.ref003","volume-title":"In StatPearls","author":"A. Naeem","year":"2022"},{"issue":"5","key":"pone.0289373.ref004","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1189\/jlb.0311134","article-title":"Lung dendritic cells at the innate-adaptive immune interface","volume":"90","author":"T. V. Condon","year":"2011","journal-title":"Journal of leukocyte biology"},{"issue":"95","key":"pone.0289373.ref005","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1183\/09059180.05.00009501","article-title":"Lung defences: an overview.","volume":"14","author":"L. P. 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Regional Office for Europe","year":"2006"},{"key":"pone.0289373.ref009","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12940-020-00575-0","article-title":"The impact of long-term PM2.5 exposure on specific causes of death: exposure-response curves and effect modification among 53 million U.S. Medicare beneficiaries.","volume":"19","author":"B. Wang","year":"2020","journal-title":"Environ Health"},{"issue":"3","key":"pone.0289373.ref010","doi-asserted-by":"crossref","first-page":"035115","DOI":"10.1063\/1.5042097","article-title":"Establishment and characterization of a multi-purpose large animal exposure chamber for investigating health effects","volume":"90","author":"X. Peng","year":"2019","journal-title":"The Review of scientific instruments"},{"key":"pone.0289373.ref011","article-title":"Aerosolized aqueous dust extracts collected near a drying lake trigger acute neutrophilic pulmonary inflammation reminiscent of microbial innate immune ligands","author":"T. A. Biddle","journal-title":"Science of The Total Environment"},{"key":"pone.0289373.ref012","article-title":"Convergent and divergent development among M cell lineages in mouse mucosal epithelium","author":"J. Wang","year":"2011","journal-title":"Journal of immunology (Baltimore, Md.: 1950)."},{"key":"pone.0289373.ref013","article-title":"Jupyter Notebooks\u2013A publishing format for reproducible computational workflows.","author":"T. 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