{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:17:05Z","timestamp":1783696625556,"version":"3.55.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF17OC0026698"],"award-info":[{"award-number":["NNF17OC0026698"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R232-2016-2425"],"award-info":[{"award-number":["R232-2016-2425"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:p> Treatment of the cigarette smoke-associated lung diseases, such as chronic obstructive pulmonary disease (COPD), has largely focused on broad-spectrum anti-inflammatory therapies. However, these therapies, such as high-dose inhaled corticosteroids, enhance patient susceptibility to lung infection and exacerbation. Our objective was to assess whether the cationic host defense peptide, human \u03b2-defensin 2 (hBD-2), can simultaneously reduce pulmonary inflammation in cigarette smoke-exposed mice while maintaining immune competence during bacterial exacerbation. Mice were exposed to cigarette smoke acutely (4 days) or chronically (5 days\/wk for 7 wk) and administered hBD-2 intranasally or by gavage. In a separate model of acute exacerbation, chronically exposed mice treated with hBD-2 were infected with nontypeable Haemophilus influenzae before euthanasia. In the acute exposure model, cigarette smoke-associated pulmonary neutrophilia was significantly blunted by both local and systemic hBD-2 administration. Similarly, chronically exposed mice administered hBD-2 therapeutically exhibited reduced pulmonary neutrophil infiltration and downregulated proinflammatory signaling in the lungs compared with vehicle-treated mice. Finally, in a model of acute bacterial exacerbation, hBD-2 administration effectively limited neutrophil infiltration in the lungs while markedly reducing pulmonary bacterial load. This study shows that hBD-2 treatment can significantly attenuate lung neutrophilia induced by cigarette smoke exposure while preserving immune competence and promoting an appropriate host-defense response to bacterial stimuli. <\/jats:p>","DOI":"10.1152\/ajplung.00027.2022","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T12:00:39Z","timestamp":1653998439000},"page":"L37-L47","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Recombinant human \u03b2-defensin 2 delivery improves smoking-induced lung neutrophilia and bacterial exacerbation"],"prefix":"10.1152","volume":"323","author":[{"given":"Nadia","family":"Milad","sequence":"first","affiliation":[{"name":"Quebec Heart and Lung Institute, Universit\u00e9 Laval, Quebec City, Quebec, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Pineault","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute, Universit\u00e9 Laval, Quebec City, Quebec, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Bouffard","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute, Universit\u00e9 Laval, Quebec City, Quebec, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u00ebl","family":"Maranda-Robitaille","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute, Universit\u00e9 Laval, Quebec City, Quebec, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Lechasseur","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute, Universit\u00e9 Laval, Quebec City, Quebec, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jos\u00e9e","family":"Beaulieu","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute, Universit\u00e9 Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Aubin","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute, Universit\u00e9 Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A. H.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-1429","authenticated-orcid":true,"given":"Mathieu C.","family":"Morissette","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute, Universit\u00e9 Laval, Quebec City, Quebec, Canada"},{"name":"Department of Medicine, Universit\u00e9 Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60968-9"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61382-8"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30293-X"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4025"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.105950"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-020-01315-3"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0058-8"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2010.06.010"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.9.5287-5289.2002"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01176"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.0019-2805.2004.01816.x"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203907200"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700599"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00093"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13766"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.636061"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2008.07.024"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14961"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00482.2018"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001182"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00681-2017"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00004314"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-1311-8"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201503-0487OC"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.2002"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1999.277.1.L97"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199600526-00005"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0492TR"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1136\/thx.51.3.267"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2003.019349"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.158.4.9802078"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.11.053"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa063070"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00081409"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajplung.00027.2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T18:27:55Z","timestamp":1656700075000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajplung.00027.2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,7,1]]}},"alternative-id":["10.1152\/ajplung.00027.2022"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00027.2022","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,1]]},"assertion":[{"value":"2022-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-17","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}