{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:08:53Z","timestamp":1792757333618,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 GM-136429"],"award-info":[{"award-number":["R35 GM-136429"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD-098363"],"award-info":[{"award-number":["R01 HD-098363"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM-116162"],"award-info":[{"award-number":["R01 GM-116162"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008328","name":"Austrian Marshall Plan Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Adenosine triphosphate (ATP) enhances neutrophil responses, but little is known about the role of ATP in influenza infections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used a mouse influenza model to study if ATP release is associated with neutrophil activation and disease progression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Influenza infection increased pulmonary ATP levels 5-fold and plasma ATP levels 3-fold vs healthy mice. Adding ATP at those concentrations to blood from healthy mice primed neutrophils and enhanced CD11b and CD63 expression, CD62L shedding, and reactive oxygen species production in response to formyl peptide receptor stimulation. Influenza infection also primed neutrophils in vivo, resulting in formyl peptide receptor\u2013induced CD11b expression and CD62L shedding up to 3 times higher than that of uninfected mice. In infected mice, large numbers of neutrophils entered the lungs. These cells were significantly more activated than the peripheral neutrophils of infected mice and pulmonary neutrophils of healthy mice. Plasma ATP levels of infected mice and influenza disease progression corresponded with the numbers and activation level of their pulmonary neutrophils.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Findings suggest that ATP release from the lungs of infected mice promotes influenza disease progression by priming peripheral neutrophils, which become strongly activated and cause pulmonary tissue damage after their recruitment to the lungs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad442","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T13:07:42Z","timestamp":1696511262000},"page":"120-130","source":"Crossref","is-referenced-by-count":9,"title":["Adenosine Triphosphate Release From Influenza-Infected Lungs Enhances Neutrophil Activation and Promotes Disease Progression"],"prefix":"10.1093","volume":"230","author":[{"given":"Carola","family":"Ledderose","sequence":"first","affiliation":[{"name":"Department of Surgery, University of California, San Diego Health"},{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria-Angeliki","family":"Valsami","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Elevado","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang G","family":"Junger","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, San Diego Health"},{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"2024072520123004000_jiad442-B1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0140-6736(17)30129-0","article-title":"Influenza","volume":"390","author":"Paules","year":"2017","journal-title":"Lancet"},{"key":"2024072520123004000_jiad442-B2","doi-asserted-by":"crossref","first-page":"e1003550","DOI":"10.1371\/journal.pmed.1003550","article-title":"Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: a systematic review and meta-analysis","volume":"18","author":"Lafond","year":"2021","journal-title":"PLoS Med"},{"key":"2024072520123004000_jiad442-B3","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/S0140-6736(22)00982-5","article-title":"Influenza","volume":"400","author":"Uyeki","year":"2022","journal-title":"Lancet"},{"key":"2024072520123004000_jiad442-B4","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S1473-3099(09)70175-6","article-title":"Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses","volume":"9","author":"Kunisaki","year":"2009","journal-title":"Lancet Infect Dis"},{"key":"2024072520123004000_jiad442-B5","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1146\/annurev.pathmechdis.3.121806.154316","article-title":"The pathology of influenza virus infections","volume":"3","author":"Taubenberger","year":"2008","journal-title":"Annu Rev Pathol"},{"key":"2024072520123004000_jiad442-B6","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1038\/nm1477","article-title":"Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia","volume":"12","author":"de Jong","year":"2006","journal-title":"Nat Med"},{"key":"2024072520123004000_jiad442-B7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S1473-3099(13)70286-X","article-title":"Pathogenesis of influenza-induced acute respiratory distress syndrome","volume":"14","author":"Short","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"2024072520123004000_jiad442-B8","doi-asserted-by":"crossref","first-page":"14933","DOI":"10.1128\/JVI.79.23.14933-14944.2005","article-title":"Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice","volume":"79","author":"Tumpey","year":"2005","journal-title":"J Virol"},{"key":"2024072520123004000_jiad442-B9","doi-asserted-by":"crossref","first-page":"7441","DOI":"10.4049\/jimmunol.0902497","article-title":"Neutrophils ameliorate lung injury and the development of severe disease during influenza infection","volume":"183","author":"Tate","year":"2009","journal-title":"J Immunol"},{"key":"2024072520123004000_jiad442-B10","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ajpath.2011.03.013","article-title":"Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis","volume":"179","author":"Narasaraju","year":"2011","journal-title":"Am J Pathol"},{"key":"2024072520123004000_jiad442-B11","doi-asserted-by":"crossref","first-page":"e17618","DOI":"10.1371\/journal.pone.0017618","article-title":"The role of neutrophils during mild and severe influenza virus infections of mice","volume":"6","author":"Tate","year":"2011","journal-title":"PLoS One"},{"key":"2024072520123004000_jiad442-B12","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1086\/591708","article-title":"Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness","volume":"198","author":"Morens","year":"2008","journal-title":"J Infect Dis"},{"key":"2024072520123004000_jiad442-B13","doi-asserted-by":"crossref","first-page":"e1000115","DOI":"10.1371\/journal.ppat.1000115","article-title":"H5n1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice","volume":"4","author":"Perrone","year":"2008","journal-title":"PLoS Pathog"},{"key":"2024072520123004000_jiad442-B14","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41590-018-0111-5","article-title":"Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza","volume":"19","author":"Dunning","year":"2018","journal-title":"Nat Immunol"},{"key":"2024072520123004000_jiad442-B15","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1038\/s41467-019-11249-y","article-title":"Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection","volume":"10","author":"Tang","year":"2019","journal-title":"Nat Commun"},{"key":"2024072520123004000_jiad442-B16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1046\/j.1365-2818.2000.00645.x","article-title":"Analysis of integrin (CD11b\/CD18) movement during neutrophil adhesion and migration on endothelial cells","volume":"197","author":"Rochon","year":"2000","journal-title":"J Microsc"},{"key":"2024072520123004000_jiad442-B17","doi-asserted-by":"crossref","first-page":"jcs250340","DOI":"10.1242\/jcs.250340","article-title":"L-selectin regulates human neutrophil transendothelial migration","volume":"134","author":"Rahman","year":"2021","journal-title":"J Cell Sci"},{"key":"2024072520123004000_jiad442-B18","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1146\/annurev-biochem-060815-014442","article-title":"Reactive oxygen species and neutrophil function","volume":"85","author":"Winterbourn","year":"2016","journal-title":"Annu Rev Biochem"},{"key":"2024072520123004000_jiad442-B19","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1111\/febs.15803","article-title":"Roles of neutrophil granule proteins in orchestrating inflammation and immunity","volume":"289","author":"Othman","year":"2022","journal-title":"FEBS J"},{"key":"2024072520123004000_jiad442-B20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nri2938","article-title":"Immune cell regulation by autocrine purinergic signalling","volume":"11","author":"Junger","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"2024072520123004000_jiad442-B21","first-page":"413","article-title":"Receptors for purines and pyrimidines","volume":"50","author":"Ralevic","year":"1998","journal-title":"Pharmacol Rev"},{"key":"2024072520123004000_jiad442-B22","doi-asserted-by":"crossref","first-page":"22650","DOI":"10.1074\/jbc.M113.476283","article-title":"Pannexin 1 channels link chemoattractant receptor signaling to local excitation and global inhibition responses at the front and back of polarized neutrophils","volume":"288","author":"Bao","year":"2013","journal-title":"J Biol Chem"},{"key":"2024072520123004000_jiad442-B23","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1126\/science.1132559","article-title":"ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors","volume":"314","author":"Chen","year":"2006","journal-title":"Science"},{"key":"2024072520123004000_jiad442-B24","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nature13085","article-title":"Nucleotide signalling during inflammation","volume":"509","author":"Idzko","year":"2014","journal-title":"Nature"},{"key":"2024072520123004000_jiad442-B25","doi-asserted-by":"crossref","first-page":"e97","DOI":"10.1097\/CCM.0000000000002052","article-title":"Systemic adenosine triphosphate impairs neutrophil chemotaxis and host defense in sepsis","volume":"45","author":"Li","year":"2017","journal-title":"Crit Care Med"},{"key":"2024072520123004000_jiad442-B26","doi-asserted-by":"crossref","first-page":"102503","DOI":"10.1016\/j.ebiom.2019.10.029","article-title":"Circulating levels of ATP is a biomarker of HIV cognitive impairment","volume":"51","author":"Velasquez","year":"2020","journal-title":"EBioMedicine"},{"key":"2024072520123004000_jiad442-B27","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00109-022-02185-4","article-title":"High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity","volume":"100","author":"da Silva","year":"2022","journal-title":"J Mol Med (Berl)"},{"key":"2024072520123004000_jiad442-B28","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.4049\/jimmunol.1700187","article-title":"Virus-triggered ATP release limits viral replication through facilitating IFN-\u03b2 production in a P2X7-dependent manner","volume":"199","author":"Zhang","year":"2017","journal-title":"J Immunol"},{"key":"2024072520123004000_jiad442-B29","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1164\/rccm.200803-455OC","article-title":"Influenza A virus inhibits alveolar fluid clearance in BALB\/c mice","volume":"178","author":"Wolk","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"2024072520123004000_jiad442-B30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-1-4939-8678-1_4","article-title":"Propagation and titration of influenza viruses","volume":"1836","author":"Karakus","year":"2018","journal-title":"Methods Mol Biol"},{"key":"2024072520123004000_jiad442-B31","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s11302-022-09842-w","article-title":"Optimized HPLC method to elucidate the complex purinergic signaling dynamics that regulate ATP, ADP, AMP, and adenosine levels in human blood","volume":"18","author":"Ledderose","year":"2022","journal-title":"Purinergic Signal"},{"key":"2024072520123004000_jiad442-B32","doi-asserted-by":"crossref","first-page":"113403","DOI":"10.1016\/j.jim.2022.113403","article-title":"Optimized flow cytometry assays to monitor neutrophil activation in human and mouse whole blood samples","volume":"512","author":"Ledderose","year":"2023","journal-title":"J Immunol Methods"},{"key":"2024072520123004000_jiad442-B33","first-page":"L1232","article-title":"Alveolar sodium and liquid transport in mice","volume":"277","author":"Icard","year":"1999","journal-title":"Am J Physiol"},{"key":"2024072520123004000_jiad442-B34","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2013.06.013","article-title":"A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection","volume":"154","author":"Brandes","year":"2013","journal-title":"Cell"},{"key":"2024072520123004000_jiad442-B35","first-page":"492","article-title":"Markers for predicting death as an outcome for mice used in infectious disease research","volume":"61","author":"Trammell","year":"2011","journal-title":"Comp Med"},{"key":"2024072520123004000_jiad442-B36","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1042\/cs0940461","article-title":"Neutrophil priming: pathophysiological consequences and underlying mechanisms","volume":"94","author":"Condliffe","year":"1998","journal-title":"Clin Sci (Lond)"},{"key":"2024072520123004000_jiad442-B37","first-page":"448","article-title":"ATP Induces transient elevations of [Ca2+]i in human neutrophils and primes these cells for enhanced O2\u2212 generation","volume":"58","author":"Kuhns","year":"1988","journal-title":"Lab Invest"},{"key":"2024072520123004000_jiad442-B38","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-022-09915-w","article-title":"ATP breakdown in plasma of children limits the antimicrobial effectiveness of their neutrophils","author":"Ledderose","year":"2023","journal-title":"Purinergic Signal"},{"key":"2024072520123004000_jiad442-B39","doi-asserted-by":"crossref","first-page":"e1004651","DOI":"10.1371\/journal.ppat.1004651","article-title":"Neutrophils: between host defence, immune modulation, and tissue injury","volume":"11","author":"Kruger","year":"2015","journal-title":"PLoS Pathog"},{"key":"2024072520123004000_jiad442-B40","doi-asserted-by":"crossref","first-page":"ra45","DOI":"10.1126\/scisignal.2000549","article-title":"Purinergic signaling: a fundamental mechanism in neutrophil activation","volume":"3","author":"Chen","year":"2010","journal-title":"Sci Signal"},{"key":"2024072520123004000_jiad442-B41","doi-asserted-by":"crossref","first-page":"399","DOI":"10.3389\/fimmu.2018.00399","article-title":"Purinergic regulation of neutrophil function","volume":"9","author":"Wang","year":"2018","journal-title":"Front Immunol"},{"key":"2024072520123004000_jiad442-B42","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1432-1033.1989.tb14722.x","article-title":"Purine and pyrimidine nucleotides potentiate activation of NADPH oxidase and degranulation by chemotactic peptides and induce aggregation of human neutrophils via G proteins","volume":"181","author":"Seifert","year":"1989","journal-title":"Eur J Biochem"},{"key":"2024072520123004000_jiad442-B43","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1182\/blood.V75.6.1324.1324","article-title":"Exposure of human neutrophils to exogenous nucleotides causes elevation in intracellular calcium, transmembrane calcium fluxes, and an alteration of a cytosolic factor resulting in enhanced superoxide production in response to FMLP and arachidonic acid","volume":"75","author":"Axtell","year":"1990","journal-title":"Blood"},{"key":"2024072520123004000_jiad442-B44","doi-asserted-by":"crossref","first-page":"e00229","DOI":"10.1128\/mBio.00229-17","article-title":"Contribution of the purinergic receptor P2X7 to development of lung immunopathology during influenza virus infection","volume":"8","author":"Leyva-Grado","year":"2017","journal-title":"mBio"},{"key":"2024072520123004000_jiad442-B45","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial DAMPs cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"2024072520123004000_jiad442-B46","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate immunity to influenza virus infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"2024072520123004000_jiad442-B47","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1096\/fj.08-119701","article-title":"Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs","volume":"23","author":"Reutershan","year":"2009","journal-title":"FASEB J"},{"key":"2024072520123004000_jiad442-B48","doi-asserted-by":"crossref","first-page":"G463","DOI":"10.1152\/ajpgi.00395.2018","article-title":"Extracellular release of ATP promotes systemic inflammation during acute pancreatitis","volume":"317","author":"Dixit","year":"2019","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2024072520123004000_jiad442-B49","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1096\/fj.14-253567","article-title":"CD39 improves survival in microbial sepsis by attenuating systemic inflammation","volume":"29","author":"Cs\u00f3ka","year":"2015","journal-title":"FASEB J"},{"key":"2024072520123004000_jiad442-B50","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1165\/rcmb.2012-0112OC","article-title":"Postinfection A77-1726 treatment improves cardiopulmonary function in H1N1 influenza-infected mice","volume":"47","author":"Aeffner","year":"2012","journal-title":"Am J Respir Cell Mol Biol"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiad442\/52769677\/jiad442.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/230\/1\/120\/58649473\/jiad442.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/230\/1\/120\/58649473\/jiad442.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T20:16:32Z","timestamp":1721938592000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/230\/1\/120\/7296051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,6]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,10,6]]},"published-print":{"date-parts":[[2024,7,25]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiad442","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7,15]]},"published":{"date-parts":[[2023,10,6]]}}}