{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:50:18Z","timestamp":1783511418998,"version":"3.55.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:00:00Z","timestamp":1554249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:00:00Z","timestamp":1554249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:00:00Z","timestamp":1554249600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>GM-CSF is important in regulating acute, persistent neutrophilic inflammation in certain settings, including lung injury. Ligand binding induces rapid internalization of the GM-CSF receptor (GM-CSFR\u03b1) complex, a process essential for signaling. Whereas GM-CSF controls many aspects of neutrophil biology, regulation of GM-CSFR\u03b1 expression is poorly understood, particularly the role of GM-CSFR\u03b1 in ligand clearance and whether signaling is sustained despite major down-regulation of GM-CSFR\u03b1 surface expression. We established a quantitative assay of GM-CSFR\u03b1 surface expression and used this, together with selective anti-GM-CSFR antibodies, to define GM-CSFR\u03b1 kinetics in human neutrophils, and in murine blood and alveolar neutrophils in a lung injury model. Despite rapid sustained ligand-induced GM-CSFR\u03b1 loss from the neutrophil surface, which persisted even following ligand removal, pro-survival effects of GM-CSF required ongoing ligand-receptor interaction. Neutrophils recruited to the lungs following LPS challenge showed initially high mGM-CSFR\u03b1 expression, which along with mGM-CSFR\u03b2 declined over 24 hr; this was associated with a transient increase in bronchoalveolar lavage fluid (BALF) mGM-CSF concentration. Treating mice in an LPS challenge model with CAM-3003, an anti-mGM-CSFR\u03b1 mAb, inhibited inflammatory cell influx into the lung and maintained the level of BALF mGM-CSF. Consistent with neutrophil consumption of GM-CSF, human neutrophils depleted exogenous GM-CSF, independent of protease activity. These data show that loss of membrane GM-CSFR\u03b1 following GM-CSF exposure does not preclude sustained GM-CSF\/GM-CSFR\u03b1 signaling and that this receptor plays a key role in ligand clearance. Hence neutrophilic activation via GM-CSFR may play an important role in neutrophilic lung inflammation even in the absence of high GM-CSF levels or GM-CSFR\u03b1 expression.<\/jats:p>","DOI":"10.1002\/jlb.3ma0918-347r","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T15:10:31Z","timestamp":1554304231000},"page":"1183-1194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Neutrophil GM-CSF receptor dynamics in acute lung injury"],"prefix":"10.1093","volume":"105","author":[{"given":"Silvia","family":"De Alessandris","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Cambridge , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G John","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison J","family":"Dodd","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jatinder K","family":"Juss","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinandan","family":"Devaprasad","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre , Utrecht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u00e2n","family":"Piper","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Killick","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic J","family":"Corkill","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E Suzanne","family":"Cohen","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aridaman","family":"Pandit","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre , Utrecht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R D J","family":"Radstake","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre , Utrecht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalind","family":"Simmonds","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M","family":"Condliffe","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Sleeman","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"Cowburn","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1834-1260","authenticated-orcid":false,"given":"Donna K","family":"Finch","sequence":"additional","affiliation":[{"name":"Respiratory, Inflammation and Autoimmunity, MedImmune Ltd. , Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin R","family":"Chilvers","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge , Cambridge, United 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granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients?","volume":"179","author":"Root","year":"1999","journal-title":"J Infect Dis"},{"key":"2023032406173584000_jlb10383-cit-0006","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1165\/rcmb.2013-0114OC","article-title":"Roles of lung epithelium in neutrophil recruitment during pneumococcal pneumonia?","volume":"50","author":"Yamamoto","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2023032406173584000_jlb10383-cit-0007","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1165\/rcmb.2005-0246OC","article-title":"Role of granulocyte macrophage colony-stimulating factor during gram-negative lung infection with Pseudomonas aeruginosa?","volume":"34","author":"Ballinger","year":"2006","journal-title":"Am J Respir Cell Mol 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