{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:20:59Z","timestamp":1792628459286,"version":"4.5.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"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.0151088","type":"journal-article","created":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T18:54:25Z","timestamp":1457636065000},"page":"e0151088","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis"],"prefix":"10.1371","volume":"11","author":[{"given":"Alessandra","family":"Cuccurullo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Lupia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"De Giuli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Bosco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Martin-Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Spatola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Turco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Montrucchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,3,10]]},"reference":[{"issue":"7","key":"ref1","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1046\/j.1538-7836.2003.00273.x","article-title":"Thrombopoietin: a tool for understanding thrombopoiesis","volume":"1","author":"K Kaushansky","year":"2003","journal-title":"J Thromb Haemost"},{"issue":"10","key":"ref2","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1182\/blood.V100.10.3457","article-title":"Recombinant human thrombopoietin: basic biology and evaluation of clinical studies","volume":"100","author":"DJ Kuter","year":"2002","journal-title":"Blood"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"390892","DOI":"10.1155\/2012\/390892","article-title":"Thrombopoietin as biomarker and mediator of cardiovascular damage in critical diseases","volume":"2012","author":"E Lupia","year":"2012","journal-title":"Mediators Inflamm"},{"issue":"6","key":"ref4","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1002\/jcb.23089","article-title":"The thrombopoietin\/MPL pathway in hematopoiesis and leukemogenesis","volume":"112","author":"FS Chou","year":"2011","journal-title":"J Cell Biochem"},{"issue":"7","key":"ref5","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1182\/blood.V87.7.2762.bloodjournal8772762","article-title":"Effects of recombinant human megakaryocyte growth and development factor on platelet activation","volume":"87","author":"G Montrucchio","year":"1996","journal-title":"Blood"},{"issue":"11","key":"ref6","doi-asserted-by":"crossref","first-page":"4664","DOI":"10.1182\/blood.V87.11.4664.bloodjournal87114664","article-title":"Thrombopoietin primes human platelet aggregation induced by shear stress and by multiple agonists","volume":"87","author":"A Oda","year":"1996","journal-title":"Blood"},{"issue":"4","key":"ref7","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1006\/bbrc.2002.6759","article-title":"Thrombopoietin induces p-selectin expression on platelets and subsequent platelet\/leukocyte interactions","volume":"292","author":"HE Tibbles","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"ref8","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/j.jacc.2006.04.106","article-title":"Thrombopoietin contributes to enhanced platelet activation in patients with unstable angina","volume":"48","author":"E Lupia","year":"2006","journal-title":"J Am Coll Cardiol"},{"issue":"7","key":"ref9","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1172\/JCI119320","article-title":"Regulation of polymorphonuclear cell activation by thrombopoietin","volume":"99","author":"MF Brizzi","year":"1997","journal-title":"J Clin Invest"},{"issue":"7","key":"ref10","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1161\/01.RES.84.7.785","article-title":"Thrombopoietin stimulates endothelial cell motility and neoangiogenesis by a platelet-activating factor-dependent mechanism","volume":"84","author":"MF Brizzi","year":"1999","journal-title":"Circulation research"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.regpep.2010.12.008","article-title":"A novel role of thrombopoietin as a physiological modulator of coronary flow","volume":"167","author":"R Ramella","year":"2011","journal-title":"Regul Pept"},{"issue":"5","key":"ref12","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s00395-010-0103-6","article-title":"Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum","volume":"105","author":"E Lupia","year":"2010","journal-title":"Basic research in cardiology"},{"issue":"3","key":"ref13","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1073\/pnas.0406008102","article-title":"A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain","volume":"102","author":"H Ehrenreich","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1471-213X-10-77","article-title":"Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system","volume":"10","author":"A Ivanova","year":"2010","journal-title":"BMC Dev Biol"},{"issue":"4","key":"ref15","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1097\/01.CCM.0000121433.61546.A0","article-title":"Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients","volume":"32","author":"SG Zakynthinos","year":"2004","journal-title":"Critical care medicine"},{"issue":"6","key":"ref16","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1111\/j.1538-7836.2009.03348.x","article-title":"Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation","volume":"7","author":"E Lupia","year":"2009","journal-title":"J Thromb Haemost"},{"issue":"1","key":"ref17","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/cc9627","article-title":"Thrombopoietin may enhance ventilator-induced lung injury","volume":"15","author":"L FV Del Sorbo","year":"2011","journal-title":"Crit Care"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.cyto.2012.05.005","article-title":"Involvement of thrombopoietin in acinar cell necrosis in L-arginine-induced acute pancreatitis in mice","volume":"60","author":"J Shen","year":"2012","journal-title":"Cytokine"},{"issue":"18","key":"ref19","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1161\/CIRCULATIONAHA.105.560250","article-title":"Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin","volume":"113","author":"K Li","year":"2006","journal-title":"Circulation"},{"issue":"1","key":"ref20","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/cvr\/cvm026","article-title":"Human thrombopoietin reduces myocardial infarct size, apoptosis, and stunning following ischaemia\/reperfusion in rats","volume":"77","author":"JE Baker","year":"2008","journal-title":"Cardiovasc Res"},{"issue":"2","key":"ref21","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1248\/bpb.27.219","article-title":"Expression of the soluble extracellular domain of human thrombopoietin receptor using a maltose-binding protein-affinity fusion system","volume":"27","author":"Q Zhang","year":"2004","journal-title":"Biological & pharmaceutical bulletin"},{"issue":"3","key":"ref22","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/jcp.1041450310","article-title":"M-07e human leukemic factor-dependent cell line provides a rapid and sensitive bioassay for the human cytokines GM-CSF and IL-3","volume":"145","author":"GC Avanzi","year":"1990","journal-title":"Journal of cellular physiology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/194927b0","article-title":"Aggregation of blood platelets by adenosine diphosphate and its reversal","volume":"194","author":"GV Born","year":"1962","journal-title":"Nature"},{"issue":"2","key":"ref24","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1182\/blood.V39.2.187.187","article-title":"Thrombocytopathia due to abnormalities in platelet release reaction\u2014studies on six unrelated patients","volume":"39","author":"HJ Weiss","year":"1972","journal-title":"Blood"},{"issue":"4","key":"ref25","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/S0002-9440(10)62329-2","article-title":"Role of lipopolysaccharide and cecal ligation and puncture on blood coagulation and inflammation in sensitive and resistant mice models","volume":"166","author":"J Corral","year":"2005","journal-title":"Am J Pathol"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nprot.2008.214","article-title":"Immunodesign of experimental sepsis by cecal ligation and puncture","volume":"4","author":"D Rittirsch","year":"2009","journal-title":"Nat Protoc"},{"issue":"3","key":"ref27","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1084\/jem.20052017","article-title":"Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia","volume":"203","author":"E Gonzalez-Rey","year":"2006","journal-title":"The Journal of experimental medicine"},{"issue":"12","key":"ref28","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1182\/blood-2002-10-3254","article-title":"Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C-deficient mice","volume":"101","author":"M Levi","year":"2003","journal-title":"Blood"},{"issue":"11","key":"ref29","doi-asserted-by":"crossref","first-page":"5625","DOI":"10.4049\/jimmunol.1301903","article-title":"Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis","volume":"191","author":"L Zou","year":"2013","journal-title":"J Immunol"},{"key":"ref30","article-title":"Toll-like Receptor 4 Is Essential to Preserving Cardiac Function and Survival in Low-grade Polymicrobial Sepsis","author":"M Zhang","year":"2014","journal-title":"Anesthesiology"},{"issue":"9","key":"ref31","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1056\/NEJMra1208623","article-title":"Severe sepsis and septic shock","volume":"369","author":"DC Angus","year":"2013","journal-title":"N Engl J Med"},{"issue":"18","key":"ref32","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1161\/01.CIR.0000017140.26466.F5","article-title":"Platelet-monocyte aggregates: bridging thrombosis and inflammation","volume":"105","author":"JE Freedman","year":"2002","journal-title":"Circulation"},{"issue":"4","key":"ref33","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.intimp.2013.06.004","article-title":"Neutrophil and platelet complexes and their relevance to neutrophil recruitment and activation","volume":"17","author":"C Page","year":"2013","journal-title":"Int Immunopharmacol"},{"issue":"9453","key":"ref34","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0140-6736(04)17667-8","article-title":"Septic shock","volume":"365","author":"D Annane","year":"2005","journal-title":"Lancet"},{"issue":"4","key":"ref35","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1160\/TH14-02-0126","article-title":"The role of platelets in sepsis","volume":"112","author":"SF de Stoppelaar","year":"2014","journal-title":"Thromb Haemost"},{"issue":"5 Suppl","key":"ref36","doi-asserted-by":"crossref","first-page":"S313","DOI":"10.1097\/00003246-200205001-00022","article-title":"Platelet function in sepsis","volume":"30","author":"JL Vincent","year":"2002","journal-title":"Critical care medicine"},{"issue":"12","key":"ref37","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1111\/j.1538-7836.2004.01009.x","article-title":"Platelet function in sepsis","volume":"2","author":"A Yaguchi","year":"2004","journal-title":"J Thromb Haemost"},{"issue":"6","key":"ref38","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1378\/chest.06-2233","article-title":"Platelet count decline: an early prognostic marker in critically ill patients with prolonged ICU stays","volume":"131","author":"D Moreau","year":"2007","journal-title":"Chest"},{"issue":"4","key":"ref39","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1097\/00003246-200204000-00005","article-title":"Time course of platelet counts in critically ill patients","volume":"30","author":"S Akca","year":"2002","journal-title":"Critical care medicine"},{"issue":"4","key":"ref40","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1007\/s00134-012-2725-7","article-title":"Immature platelet fraction in predicting sepsis in critically ill patients","volume":"39","author":"RA De Blasi","year":"2012","journal-title":"Intensive care medicine"},{"issue":"2","key":"ref41","first-page":"482","article-title":"The role of platelets in the adult respiratory distress syndrome. Culprits or bystanders?","volume":"135","author":"JE Heffner","year":"1987","journal-title":"Am Rev Respir Dis"},{"issue":"11","key":"ref42","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/j.1365-2362.1995.tb01694.x","article-title":"Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure","volume":"25","author":"M Gawaz","year":"1995","journal-title":"Eur J Clin Invest"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/00024382-200204000-00004","article-title":"Platelet and leukocyte activation correlate with the severity of septic organ dysfunction","volume":"17","author":"S Russwurm","year":"2002","journal-title":"Shock"},{"issue":"4","key":"ref44","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s001340050344","article-title":"Platelet function in septic multiple organ dysfunction syndrome","volume":"23","author":"M Gawaz","year":"1997","journal-title":"Intensive care medicine"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1161\/01.RES.8.1.234","article-title":"Immediate effects of intravenous endotoxin on serotonin concentrations and blood platelets","volume":"8","author":"RB Davis","year":"1960","journal-title":"Circulation research"},{"issue":"10","key":"ref46","doi-asserted-by":"crossref","first-page":"5186","DOI":"10.1128\/IAI.67.10.5186-5191.1999","article-title":"Complement-dependent accumulation and degradation of platelets in the lung and liver induced by injection of lipopolysaccharides","volume":"67","author":"M Shibazaki","year":"1999","journal-title":"Infect Immun"},{"issue":"1","key":"ref47","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4161\/viru.26482","article-title":"Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock","volume":"5","author":"D De Backer","year":"2014","journal-title":"Virulence"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"B Engelmann","year":"2013","journal-title":"Nat Rev Immunol"},{"issue":"11","key":"ref49","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1007\/s00134-010-1969-3","article-title":"Impaired microvascular perfusion in sepsis requires activated coagulation and P-selectin-mediated platelet adhesion in capillaries","volume":"36","author":"D Secor","year":"2010","journal-title":"Intensive care"},{"issue":"2","key":"ref50","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/10739680500466343","article-title":"Platelet recruitment in the murine hepatic microvasculature during experimental sepsis: role of neutrophils","volume":"13","author":"G Singer","year":"2006","journal-title":"Microcirculation"},{"issue":"5","key":"ref51","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/SLA.0b013e3181bd95b7","article-title":"Platelet-derived CD40L (CD154) mediates neutrophil upregulation of Mac-1 and recruitment in septic lung injury","volume":"250","author":"M Rahman","year":"2009","journal-title":"Ann Surg"},{"key":"ref52","article-title":"Platelet secretion of CXCL4 is Rac1-dependent and regulates neutrophil infiltration and tissue damage in septic lung damage","author":"R Hwaiz","year":"2015","journal-title":"British journal of pharmacology"},{"issue":"12","key":"ref53","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1172\/JCI29499","article-title":"Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation","volume":"116","author":"A Zarbock","year":"2006","journal-title":"J Clin Invest"},{"issue":"1","key":"ref54","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/09537100802503368","article-title":"Anti-platelet drugs and outcome in severe infection: clinical impact and underlying mechanisms","volume":"20","author":"J Winning","year":"2009","journal-title":"Platelets"},{"issue":"6","key":"ref55","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1111\/j.1538-7836.2009.03352.x","article-title":"Beneficial effect of clopidogrel in a mouse model of polymicrobial sepsis","volume":"7","author":"M Seidel","year":"2009","journal-title":"J Thromb Haemost"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/s13054-015-1091-6","article-title":"Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome","volume":"19","author":"P Toner","year":"2015","journal-title":"Crit Care"},{"issue":"3","key":"ref57","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1097\/CCM.0b013e31819b8371","article-title":"Therapeutic effects of erythropoietin in murine models of endotoxin shock","volume":"37","author":"K Aoshiba","year":"2009","journal-title":"Critical care medicine"},{"issue":"6","key":"ref58","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1055\/s-0037-1613944","article-title":"Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis?","volume":"83","author":"CC Folman","year":"2000","journal-title":"Thromb Haemost"},{"issue":"5","key":"ref59","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1089\/10799900050023915","article-title":"Interleukin-6 increases thrombopoietin production in human hepatoma cells HepG2 and Hep3B","volume":"20","author":"EM Wolber","year":"2000","journal-title":"J Interferon Cytokine Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0151088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:05:16Z","timestamp":1600301116000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0151088"}},"subtitle":[],"editor":[{"given":"Emilio","family":"Hirsch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,3,10]]},"references-count":59,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0151088","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,10]]}}}