{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:21:30Z","timestamp":1779142890138,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Asthma is a chronic disease that displays heterogeneous clinical and molecular features. A phenotypic subset of late\u2010onset severe asthmatics has debilitating fixed airflow obstruction, increased neutrophilic inflammation and a history of pneumonia. Influenza A virus (IAV) is an important viral cause of pneumonia and asthmatics are frequently hospitalised during IAV epidemics. This study aims to determine whether antagonising granulocyte colony stimulating factor receptor (G\u2010CSFR) prevents pneumonia\u2010associated severe asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Mice were sensitised to house dust mite (HDM) to establish allergic airway inflammation and subsequently infected with IAV (HKx31\/H3N2 subtype). A neutralising monoclonal antibody against G\u2010CSFR was therapeutically administered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In IAV\u2010infected mice with prior HDM sensitisation, a significant increase in airway fibrotic remodelling and airways hyper\u2010reactivity was observed. A mixed granulocytic inflammatory profile consisting of neutrophils, macrophages and eosinophils was prominent and at a molecular level, G\u2010CSF expression was significantly increased in HDMIAV\u2010treated mice. Blockage of G\u2010CSFR reduced neutrophilic inflammation in the bronchoalveolar and lungs by over 80% in HDMIAV\u2010treated mice without altering viral clearance. Markers of NETosis (dsDNA and myeloperoxidase in bronchoalveolar), tissue injury (LDH activity in bronchoalveolar) and oedema (total bronchoalveolar\u2010fluid protein) were also significantly reduced with anti\u2010G\u2010CSFR treatment. In addition, anti\u2010G\u2010CSFR antagonism significantly reduced bronchoalveolar gelatinase activity, active TFG\u03b2 lung levels, collagen lung expression, airways fibrosis and airways hyper\u2010reactivity in HDMIAV\u2010treated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>We have shown that antagonising G\u2010CSFR\u2010dependent neutrophilic inflammation reduced pathological disruption of the mucosal barrier and airways fibrosis in an IAV\u2010induced severe asthma model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15415","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T14:15:58Z","timestamp":1613830558000},"page":"1869-1885","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["G\u2010CSFR antagonism reduces mucosal injury and airways fibrosis in a virus\u2010dependent model of severe asthma"],"prefix":"10.1111","volume":"178","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Aloe","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"McQualter","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica","family":"Papanicolaou","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8443-7071","authenticated-orcid":false,"given":"Ross","family":"Vlahos","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick","family":"Wilson","sequence":"additional","affiliation":[{"name":"CSL Limited  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Bozinovski","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.129"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01359-2015"},{"issue":"1","key":"e_1_2_12_4_1","first-page":"S1","article-title":"The concise guide to pharmacology 2019\/20: Introduction and other protein targets","volume":"176","author":"Alexander S. 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