{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:03:35Z","timestamp":1791173015841,"version":"4.1.0"},"reference-count":36,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Immunology"],"published-print":{"date-parts":[[2011,1]]},"DOI":"10.1016\/j.humimm.2010.09.009","type":"journal-article","created":{"date-parts":[[2010,10,2]],"date-time":"2010-10-02T04:41:49Z","timestamp":1285994509000},"page":"54-62","source":"Crossref","is-referenced-by-count":50,"title":["TLR4 upregulation underpins airway neutrophilia in smokers with chronic obstructive pulmonary disease and acute respiratory failure"],"prefix":"10.1016","volume":"72","author":[{"given":"Elisabetta","family":"Pace","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Giarratano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreina","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liboria","family":"Siena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Mangione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gjomarkaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.humimm.2010.09.009_bib1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1513\/pats.200701-002FM","article-title":"The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research","volume":"4","author":"Curtis","year":"2007","journal-title":"Proc Am Thorac Soc"},{"key":"10.1016\/j.humimm.2010.09.009_bib2","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S0140-6736(07)61382-8","article-title":"COPD exacerbations: defining their cause and prevention","volume":"370","author":"Wedzicha","year":"2007","journal-title":"Lancet"},{"key":"10.1016\/j.humimm.2010.09.009_bib3","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1128\/CMR.14.2.336-363.2001","article-title":"Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review","volume":"14","author":"Sethi","year":"2001","journal-title":"Clin Microbiol Rev"},{"key":"10.1016\/j.humimm.2010.09.009_bib4","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1056\/NEJMoa032158","article-title":"The nature of small-airway obstruction in chronic obstructive pulmonary disease","volume":"350","author":"Hogg","year":"2004","journal-title":"N Engl J Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib5","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1136\/thx.2004.024463","article-title":"Inflammatory cells in the airways in COPD","volume":"61","author":"O'Donnell","year":"2006","journal-title":"Thorax"},{"key":"10.1016\/j.humimm.2010.09.009_bib6","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S0962-8924(01)02004-9","article-title":"Toll receptors in innate immunity","volume":"11","author":"Imler","year":"2001","journal-title":"Trends Cell Biol"},{"key":"10.1016\/j.humimm.2010.09.009_bib7","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/35021228","article-title":"Toll-like receptors in the induction of the innate immune response","volume":"406","author":"Aderem","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.humimm.2010.09.009_bib8","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1677\/JOE-07-0067","article-title":"Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease","volume":"193","author":"Mitchell","year":"2007","journal-title":"J Endocrinol"},{"key":"10.1016\/j.humimm.2010.09.009_bib9","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1172\/JCI28139","article-title":"Toll-like receptor 4 deficiency causes pulmonary emphysema","volume":"116","author":"Zhang","year":"2006","journal-title":"J Clin Invest"},{"key":"10.1016\/j.humimm.2010.09.009_bib10","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.0019-2805.2004.01816.x","article-title":"Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils","volume":"111","author":"Niyonsaba","year":"2004","journal-title":"Immunology"},{"key":"10.1016\/j.humimm.2010.09.009_bib11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1465-9921-6-68","article-title":"Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients","volume":"6","author":"Droemann","year":"2005","journal-title":"Respir Res"},{"key":"10.1016\/j.humimm.2010.09.009_bib12","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1465-9921-7-64","article-title":"Expression of toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease","volume":"7","author":"Pons","year":"2006","journal-title":"Respir Res"},{"key":"10.1016\/j.humimm.2010.09.009_bib13","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1164\/ajrccm.163.5.2101039","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease","volume":"163","author":"Pauwels","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib14","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1365-2249.2003.02387.x","article-title":"LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space","volume":"135","author":"Pace","year":"2004","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.humimm.2010.09.009_bib15","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1164\/ajrccm.159.5.9806001","article-title":"Interleukin-8 induces lymphocyte chemotaxis within the pleural space that is regulated by pleural macrophages","volume":"159","author":"Pace","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib16","doi-asserted-by":"crossref","first-page":"J2005","DOI":"10.1183\/09031936.05.00092404","article-title":"Does leptin play a cytokine-like role within the airways of COPD patients?","volume":"26","author":"Bruno","year":"2005","journal-title":"Eur Respir J"},{"key":"10.1016\/j.humimm.2010.09.009_bib17","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1365-2567.2007.02788.x","article-title":"Cigarette smoke increases TLR4 and modifies LPS mediated responses in airway epithelial cells","volume":"124","author":"Pace","year":"2008","journal-title":"Immunology"},{"key":"10.1016\/j.humimm.2010.09.009_bib18","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.4049\/jimmunol.177.10.7155","article-title":"Lipopolysaccharide-activated CD4+CD25+ T regulatory cells inhibit neutrophil function and promote their apoptosis and death","volume":"177","author":"Lewkowicz","year":"2006","journal-title":"J Immunol"},{"key":"10.1016\/j.humimm.2010.09.009_bib19","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1164\/rccm.200208-794OC","article-title":"Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease","volume":"168","author":"Qiu","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib20","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1164\/ajrccm.160.supplement_1.4","article-title":"Granulocyte apoptosis and its role in the resolution and control of lung inflammation","volume":"160","author":"Haslett","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib21","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1465-9921-10-24","article-title":"Dysregulated apoptosis and NF\u03baB expression in COPD subjects","volume":"10","author":"Brown","year":"2009","journal-title":"Respir Res"},{"key":"10.1016\/j.humimm.2010.09.009_bib22","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1126\/science.1075565","article-title":"Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin","volume":"298","author":"Biragyn","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.humimm.2010.09.009_bib23","doi-asserted-by":"crossref","first-page":"142S","DOI":"10.1378\/chest.121.5_suppl.142S","article-title":"Airways inflammation and COPD: Epithelial-neutrophil interactions","volume":"121","author":"Pettersen","year":"2002","journal-title":"Chest"},{"key":"10.1016\/j.humimm.2010.09.009_bib24","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.rmed.2007.08.013","article-title":"Upregulation of ICAM-1 expression in bronchial epithelial cells by airway secretions in bronchiectasis","volume":"102","author":"Chan","year":"2008","journal-title":"Respir Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib25","doi-asserted-by":"crossref","first-page":"L479","DOI":"10.1152\/ajplung.00518.2005","article-title":"Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial cells","volume":"291","author":"Boodoo","year":"2006","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.humimm.2010.09.009_bib26","doi-asserted-by":"crossref","first-page":"37692","DOI":"10.1074\/jbc.M105927200","article-title":"Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells","volume":"276","author":"Re","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.humimm.2010.09.009_bib27","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1164\/rccm.200606-777PP","article-title":"Targeting the networks that underpin contiguous immunity in asthma and chronic obstructive pulmonary disease","volume":"175","author":"Sabroe","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib28","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1084\/jem.20031023","article-title":"LPS-TLR4 signaling to IRF-3\/7 and NF-kappaB involves the toll adapters TRAM and trif","volume":"198","author":"Fitzgerald","year":"2003","journal-title":"J Exp Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib29","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nri1630","article-title":"Negative regulation of toll-like receptor-mediated immune responses","volume":"5","author":"Liew","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.humimm.2010.09.009_bib30","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1164\/rccm.2107139","article-title":"Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease","volume":"165","author":"Saetta","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib31","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1164\/ajrccm.155.3.9117016","article-title":"Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1","volume":"155","author":"O'Shaughnessy","year":"1997","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib32","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1164\/ajrccm.157.3.9709027","article-title":"CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease","volume":"157","author":"Saetta","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.humimm.2010.09.009_bib33","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1365-2249.2007.03451.x","article-title":"Increased intracellular T helper 1 proinflammatory cytokine production in peripheral blood, bronchoalveolar lavage and intraepithelial T cells of COPD subjects","volume":"150","author":"Hodge","year":"2007","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.humimm.2010.09.009_bib34","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1183\/09031936.00010407","article-title":"Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco smoking","volume":"31","author":"Barcel\u00f3","year":"2008","journal-title":"Eur Respir J"},{"key":"10.1016\/j.humimm.2010.09.009_bib35","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1378\/chest.124.5.1909","article-title":"Marked up-regulation of T lymphocytes and expression of interleukin-9 in bronchial biopsies from patients with chronic bronchitis with obstruction","volume":"124","author":"Panzner","year":"2003","journal-title":"Chest"},{"key":"10.1016\/j.humimm.2010.09.009_bib36","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.molimm.2009.11.008","article-title":"Differential gene expression analysis in human monocyte-derived macrophages: impact of cigarette smoke on host defence","volume":"47","author":"Doyle","year":"2010","journal-title":"Mol Immunol"}],"container-title":["Human Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0198885910005021?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0198885910005021?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T12:23:49Z","timestamp":1544185429000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0198885910005021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1]]}},"alternative-id":["S0198885910005021"],"URL":"https:\/\/doi.org\/10.1016\/j.humimm.2010.09.009","relation":{},"ISSN":["0198-8859"],"issn-type":[{"value":"0198-8859","type":"print"}],"subject":[],"published":{"date-parts":[[2011,1]]}}}