{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:57:52Z","timestamp":1777654672761,"version":"3.51.4"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T00:00:00Z","timestamp":1430265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0124593","type":"journal-article","created":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T18:22:33Z","timestamp":1430331753000},"page":"e0124593","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Delivery of GM-CSF to Protect against Influenza Pneumonia"],"prefix":"10.1371","volume":"10","author":[{"given":"Renuka","family":"Subramaniam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary","family":"Hillberry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalyn","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Neuenschwander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Homayoun","family":"Shams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,4,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1086\/590567","article-title":"The 1918 &quot;Spanish flu&quot; in Spain","volume":"47","author":"A Trilla","year":"2008","journal-title":"Clin Infect Dis"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1164\/rccm.201012-2036OC","article-title":"GM-CSF in the lung protects against lethal influenza infection","volume":"184","author":"FF Huang","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.4049\/jimmunol.1300014","article-title":"Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections","volume":"191","author":"HE Ghoneim","year":"2013","journal-title":"J Immunol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"e1004053","DOI":"10.1371\/journal.ppat.1004053","article-title":"Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection","volume":"10","author":"C Schneider","year":"2014","journal-title":"PLoS Pathog"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1172\/JCI62139","article-title":"Alveolar epithelial cells orchestrate DC function in murine viral pneumonia","volume":"122","author":"B Unkel","year":"2012","journal-title":"J Clin Invest"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1093\/infdis\/jit830","article-title":"Protecting against post-influenza bacterial pneumonia by increasing phagocyte recruitment and ROS production","volume":"209","author":"R Subramaniam","year":"2014","journal-title":"J Infect Dis"},{"key":"ref7","first-page":"L715","article-title":"GM-CSF enhances lung growth and causes alveolar type II epithelial cell hyperplasia in transgenic mice","volume":"273","author":"Reed JA Huffman","year":"1997","journal-title":"Am J Physiol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1172\/JCI118461","article-title":"Pulmonary epithelial cell expression of GM-CSF corrects the alveolar proteinosis in GM-CSF-deficient mice","volume":"97","author":"JA Huffman","year":"1996","journal-title":"J Clin Invest"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1067\/mai.2003.1460","article-title":"Effect of GM-CSF on immune, inflammatory, and clinical responses to ragweed in a novel mouse model of mucosal sensitization","volume":"111","author":"EC Cates","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.4049\/jimmunol.180.4.2600","article-title":"Granulocyte-macrophage colony-stimulating factor is required for bronchial eosinophilia in a murine model of allergic airway inflammation","volume":"180","author":"YC Su","year":"2008","journal-title":"J Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/S0008-8749(02)00565-8","article-title":"Attenuation of airway hyperresponsiveness in a murine asthma model by neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF)","volume":"219","author":"N Yamashita","year":"2002","journal-title":"Cell Immunol"},{"key":"ref12","first-page":"L556","article-title":"Aerosolized GM-CSF ameliorates pulmonary alveolar proteinosis in GM-CSF-deficient mice","volume":"276","author":"JA Reed","year":"1999","journal-title":"Am J Physiol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1164\/rccm.200406-716OC","article-title":"Granulocyte-macrophage colony-stimulating factor and lung immunity in pulmonary alveolar proteinosis","volume":"171","author":"R Tazawa","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"ref14","article-title":"Duration of benefit in patients with autoimmune pulmonary alveolar proteinosis after inhaled GM-CSF therapy","author":"R Tazawa","year":"2013","journal-title":"Chest"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1164\/rccm.201311-2041LE","article-title":"Inhaled granulocyte\/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome","volume":"189","author":"S Herold","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/CCM.0b013e31822d7bf0","article-title":"A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury","volume":"40","author":"III Paine R","year":"2012","journal-title":"Crit Care Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"207","DOI":"10.33549\/physiolres.930606","article-title":"Action of granulopoiesis-stimulating cytokines rhG-CSF, rhGM-CSF, and rmGM-CSF on murine haematopoietic progenitor cells for granulocytes and macrophages (GM-CFC)","volume":"54","author":"M Hofer","year":"2005","journal-title":"Physiol Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S1074-7613(01)00218-7","article-title":"GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1","volume":"15","author":"Y Shibata","year":"2001","journal-title":"Immunity"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1001\/jama.289.2.179","article-title":"Mortality associated with influenza and respiratory syncytial virus in the United States","volume":"289","author":"WW Thompson","year":"2003","journal-title":"JAMA"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.4049\/jimmunol.165.1.49","article-title":"Polyethylene glycol-modified GM-CSF expands CD11b(high)CD11c(high) but notCD11b(low)CD11c(high) murine dendritic cells in vivo: a comparative analysis with Flt3 ligand","volume":"165","author":"E Daro","year":"2000","journal-title":"J Immunol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1073\/pnas.86.4.1213","article-title":"Hematopoietic activity of granulocyte\/macrophage colony-stimulating factor is dependent upon two distinct regions of the molecule: functional analysis based upon the activities of interspecies hybrid growth factors","volume":"86","author":"K Kaushansky","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1126\/science.3296190","article-title":"The human hematopoietic colony-stimulating factors","volume":"236","author":"SC Clark","year":"1987","journal-title":"Science"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1182\/blood.V98.10.3165","article-title":"Perverted responses of the human granulocyte-macrophage colony-stimulating factor receptor in mouse cell lines due to cross-species beta-subunit association","volume":"98","author":"B McClure","year":"2001","journal-title":"Blood"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1182\/blood.V67.2.257.257","article-title":"The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors","volume":"67","author":"D Metcalf","year":"1986","journal-title":"Blood"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/0092-8674(91)90040-6","article-title":"A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF","volume":"66","author":"J Tavernier","year":"1991","journal-title":"Cell"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cyto.2010.04.001","article-title":"Protective effects of recombinant human granulocyte macrophage colony stimulating factor on H1N1 influenza virus-induced pneumonia in mice","volume":"51","author":"H Huang","journal-title":"Cytokine"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.4049\/jimmunol.164.5.2602","article-title":"Granulocyte-macrophage colony-stimulating factor in the innate immune response to Pneumocystis carinii pneumonia in mice","volume":"164","author":"III Paine R","year":"2000","journal-title":"J Immunol"},{"key":"ref28","article-title":"Protecting against post-influenza bacterial pneumonia by increasing phagocyte recruitment and ROS production","author":"R Subramaniam","year":"2013","journal-title":"J Infect Dis"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.4049\/jimmunol.180.4.2562","article-title":"CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality","volume":"180","author":"KL Lin","year":"2008","journal-title":"J Immunol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1126\/science.1233632","article-title":"Role of tissue protection in lethal respiratory viral-bacterial coinfection","volume":"340","author":"AM Jamieson","year":"2013","journal-title":"Science"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1002\/j.1460-2075.1985.tb03971.x","article-title":"Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes","volume":"4","author":"S Miyatake","year":"1985","journal-title":"EMBO J"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"6250","DOI":"10.1073\/pnas.82.18.6250","article-title":"Cloning, sequence, and expression of a human granulocyte\/macrophage colony-stimulating factor","volume":"82","author":"MA Cantrell","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI113316","article-title":"Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony-stimulating factors. Mechanism for the hematopoietic response to inflammation","volume":"81","author":"K Kaushansky","year":"1988","journal-title":"J Clin Invest"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1073\/pnas.86.13.4872","article-title":"Identification of critical regions in mouse granulocyte-macrophage colony-stimulating factor by scanning-deletion analysis","volume":"86","author":"AB Shanafelt","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Nishijima I (1997) Human granulocyte-macrophage colony-stimulating factor (hGM-CSF)-dependent in vitro and in vivo proliferation and differentiation of all hematopoietic progenitor cells in hGM-CSF receptor transgenic mice.","DOI":"10.1016\/S0091-6749(97)70011-3"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11248-011-9513-y","article-title":"Expression of hGM-CSF in silk glands of transgenic silkworms using gene targeting vector","volume":"21","author":"R Xue","year":"2012","journal-title":"Transgenic Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.ejps.2006.02.014","article-title":"Can 29kDa rhGM-CSF expressed by silkworm pupae bioreactor bring into effect as active cytokine through orally administration?","volume":"28","author":"Y Zhang","journal-title":"Eur J Pharm Sci"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1177\/1099800410378160","article-title":"Treatment of skin injury due to vinorelbine extravasation using bFGF and rhGM-CSF: an experimental study in a murine model","volume":"13","author":"C Yu","year":"2011","journal-title":"Biol Res Nurs"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1126\/science.1837174","article-title":"Novel fold and putative receptor binding site of granulocyte-macrophage colony-stimulating factor","volume":"254","author":"K Diederichs","year":"1991","journal-title":"Science"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e4176","DOI":"10.1371\/journal.pone.0004176","article-title":"Augmented lung inflammation protects against influenza A pneumonia","volume":"4","author":"MJ Tuvim","year":"2009","journal-title":"PLoS ONE"},{"issue":"7 Suppl","key":"ref41","first-page":"94","article-title":"Aging and impaired immunity to influenza viruses: implications for vaccine development","author":"WM Liu","year":"2011","journal-title":"Hum Vaccin"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"8077","DOI":"10.1016\/j.vaccine.2010.10.023","article-title":"Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans","volume":"28","author":"D Frasca","year":"2010","journal-title":"Vaccine"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.arr.2010.08.004","article-title":"Age effects on B cells and humoral immunity in humans","volume":"10","author":"D Frasca","year":"2011","journal-title":"Ageing Res Rev"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.coi.2014.05.008","article-title":"B cell function and influenza vaccine responses in healthy aging and disease","volume":"29","author":"D Frasca","journal-title":"Curr Opin Immunol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e34681","DOI":"10.1371\/journal.pone.0034681","article-title":"Deletion of FoxN1 in the thymic medullary epithelium reduces peripheral T cell responses to infection and mimics changes of aging","volume":"7","author":"J Guo","year":"2012","journal-title":"PLoS ONE"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/biot.200900218","article-title":"PEGylation of therapeutic proteins","volume":"5","author":"S Jevsevar","year":"2010","journal-title":"Biotechnol J"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nrgastro.2010.101","article-title":"Pegylated interferons alpha2a and alpha2b in the treatment of chronic hepatitis C","volume":"7","author":"A Aghemo","year":"2010","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.antiviral.2003.08.015","article-title":"Pegylated interferons for chronic hepatitis B","volume":"60","author":"A Craxi","year":"2003","journal-title":"Antiviral Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0124593","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T22:20:53Z","timestamp":1691619653000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0124593"}},"subtitle":[],"editor":[{"given":"Jie","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,4,29]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0124593","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,29]]}}}