{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:47:15Z","timestamp":1788871635926,"version":"build-2803163510"},"reference-count":38,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":3597,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"name":"ZonMW","award":["92003504"],"award-info":[{"award-number":["92003504"]}]},{"name":"Stichting BeGeTu"},{"DOI":"10.13039\/501100003246","name":"Netherlands Organisation for Scientific Research","doi-asserted-by":"crossref","award":["91610008"],"award-info":[{"award-number":["91610008"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["jthjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thrombosis and Haemostasis"],"published-print":{"date-parts":[[2013,2]]},"DOI":"10.1111\/jth.12094","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T12:51:12Z","timestamp":1355230272000},"page":"282-292","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"title":["Endogenous protein C has a protective role during Gram\u2010negative pneumosepsis (melioidosis)"],"prefix":"10.1016","volume":"11","author":[{"given":"L.M.","family":"Kager","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.J.","family":"Wiersinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.J.","family":"Roelofs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.C.M.","family":"Meijers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.S.","family":"Zeerleder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.T.","family":"Esmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"van 't Veer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"van der Poll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl 1","key":"10.1111\/jth.12094_bb0010","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1055\/s-2006-939554","article-title":"Inflammation and the activated protein C anticoagulant pathway","volume":"32","author":"Esmon","year":"2006","journal-title":"Semin Thromb Hemost"},{"key":"10.1111\/jth.12094_bb0015","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1182\/blood-2006-09-003004","article-title":"The cytoprotective protein C pathway","volume":"109","author":"Mosnier","year":"2007","journal-title":"Blood"},{"key":"10.1111\/jth.12094_bb0020","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1182\/blood-2009-09-201616","article-title":"The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications","volume":"115","author":"Danese","year":"2010","journal-title":"Blood"},{"key":"10.1111\/jth.12094_bb0025","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1165\/rcmb.2009-0223OC","article-title":"Differential effects of sphingosine 1\u2010phosphate receptors on airway and vascular barrier function in the murine lung","volume":"43","author":"Sammani","year":"2010","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1111\/jth.12094_bb0030","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nri2974","article-title":"The outs and the ins of sphingosine\u20101\u2010phosphate in immunity","volume":"11","author":"Spiegel","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"10.1111\/jth.12094_bb0035","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1182\/blood-2004-10-3985","article-title":"Endothelial barrier protection by activated protein C through PAR1\u2010dependent sphingosine 1\u2010phosphate receptor\u20101 crossactivation","volume":"105","author":"Feistritzer","year":"2005","journal-title":"Blood"},{"key":"10.1111\/jth.12094_bb0040","doi-asserted-by":"crossref","first-page":"17286","DOI":"10.1074\/jbc.M412427200","article-title":"Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1\u2010phosphate receptor transactivation","volume":"280","author":"Finigan","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1111\/jth.12094_bb0045","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1164\/rccm.200405-684OC","article-title":"Sphingosine 1\u2010phosphate reduces vascular leak in murine and canine models of acute lung injury","volume":"170","author":"McVerry","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1111\/jth.12094_bb0050","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1164\/rccm.200309-1258OC","article-title":"Protective effects of sphingosine 1\u2010phosphate in murine endotoxin\u2010induced inflammatory lung injury","volume":"169","author":"Peng","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1111\/jth.12094_bb0055","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/nm.2053","article-title":"Extracellular histones are major mediators of death in sepsis","volume":"15","author":"Xu","year":"2009","journal-title":"Nat Med"},{"key":"10.1111\/jth.12094_bb0060","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jcrc.2011.05.006","article-title":"Severe protein C deficiency is associated with organ dysfunction in patients with severe sepsis","volume":"26","author":"Shaw","year":"2011","journal-title":"J Crit Care"},{"key":"10.1111\/jth.12094_bb0065","doi-asserted-by":"crossref","first-page":"S223","DOI":"10.1097\/01.CCM.0000126120.49367.AC","article-title":"Severe protein C deficiency predicts early death in severe sepsis","volume":"32","author":"Macias","year":"2004","journal-title":"Crit Care Med"},{"key":"10.1111\/jth.12094_bb0070","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1097\/00003246-200009001-00011","article-title":"Protein C levels as a prognostic indicator of outcome in sepsis and related diseases","volume":"28","author":"Fisher","year":"2000","journal-title":"Crit Care Med"},{"key":"10.1111\/jth.12094_bb0075","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1182\/blood-2004-03-1203","article-title":"Patients with severe sepsis vary markedly in their ability to generate activated protein C","volume":"104","author":"Liaw","year":"2004","journal-title":"Blood"},{"key":"10.1111\/jth.12094_bb0080","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1182\/blood-2002-10-3254","article-title":"Aggravation of endotoxin\u2010induced disseminated intravascular coagulation and cytokine activation in heterozygous protein\u2010C\u2010deficient mice","volume":"101","author":"Levi","year":"2003","journal-title":"Blood"},{"key":"10.1111\/jth.12094_bb0085","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1182\/blood-2006-07-037945","article-title":"Acute inflammation is exacerbated in mice genetically predisposed to a severe protein C deficiency","volume":"109","author":"Lay","year":"2007","journal-title":"Blood"},{"key":"10.1111\/jth.12094_bb0090","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1111\/j.1538-7836.2011.04199.x","article-title":"Endogenous protein C inhibits activation of coagulation and transiently lowers bacterial outgrowth in murine Escherichia coli peritonitis","volume":"9","author":"Schouten","year":"2011","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.12094_bb0095","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1165\/rcmb.2010-0370OC","article-title":"Impact of endogenous protein C on pulmonary coagulation and injury during lethal H1N1 influenza in mice","volume":"45","author":"Schouten","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1111\/jth.12094_bb0100","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/j.1538-7836.2009.03333.x","article-title":"Endogenous activated protein C signaling is critical to protection of mice from lipopolysaccaride\u2010induced septic shock","volume":"7","author":"Xu","year":"2009","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.12094_bb0105","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1111\/j.1538-7836.2011.04473.x","article-title":"Plasminogen activator inhibitor type I contributes to protective immunity during experimental Gram\u2010negative sepsis (melioidosis)","volume":"9","author":"Kager","year":"2011","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.12094_bb0110","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1097\/CCM.0b013e31824ea05e","article-title":"Endogenous tissue\u2010type plasminogen activator impairs host defense during severe experimental gram\u2010negative sepsis (melioidosis)","volume":"40","author":"Kager","year":"2012","journal-title":"Crit Care Med"},{"key":"10.1111\/jth.12094_bb0115","doi-asserted-by":"crossref","first-page":"e248","DOI":"10.1371\/journal.pmed.0040248","article-title":"Toll\u2010like receptor 2 impairs host defense in gram\u2010negative sepsis caused by Burkholderia pseudomallei (Melioidosis)","volume":"4","author":"Wiersinga","year":"2007","journal-title":"PLoS Med"},{"key":"10.1111\/jth.12094_bb0120","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/cid\/cir808","article-title":"Clinical features and epidemiology of melioidosis pneumonia: results from a 21\u2010year study and review of the literature","volume":"54","author":"Meumann","year":"2012","journal-title":"Clin Infect Dis"},{"key":"10.1111\/jth.12094_bb0125","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/S0140-6736(03)13374-0","article-title":"Melioidosis","volume":"361","author":"White","year":"2003","journal-title":"Lancet"},{"key":"10.1111\/jth.12094_bb0130","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nrmicro1385","article-title":"Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei","volume":"4","author":"Wiersinga","year":"2006","journal-title":"Nat Rev Microbiol"},{"key":"10.1111\/jth.12094_bb0135","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1538-7836.2007.02796.x","article-title":"Activation of coagulation with concurrent impairment of anticoagulant mechanisms correlates with a poor outcome in severe melioidosis","volume":"6","author":"Wiersinga","year":"2008","journal-title":"J Thromb Haemost"},{"key":"10.1111\/jth.12094_bb0140","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijid.2005.06.001","article-title":"Decreased protein C, protein S, and antithrombin levels are predictive of poor outcome in Gram\u2010negative sepsis caused by Burkholderia pseudomallei","volume":"10","author":"LaRosa","year":"2006","journal-title":"Int J Infect Dis"},{"key":"10.1111\/jth.12094_bb0145","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1182\/blood-2009-04-217679","article-title":"Endogenous activated protein C limits cancer cell extravasation through sphingosine\u20101\u2010phosphate receptor 1\u2010mediated vascular endothelial barrier enhancement","volume":"114","author":"van Sluis","year":"2009","journal-title":"Blood"},{"key":"10.1111\/jth.12094_bb0150","doi-asserted-by":"crossref","first-page":"F1516","DOI":"10.1152\/ajprenal.00311.2005","article-title":"Selective sphingosine 1\u2010phosphate 1 receptor activation reduces ischemia\u2010reperfusion injury in mouse kidney","volume":"290","author":"Awad","year":"2006","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.1111\/jth.12094_bb0155","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1016\/j.febslet.2007.10.037","article-title":"A plasma nucleosome releasing factor (NRF) with serine protease activity is instrumental in removal of nucleosomes from secondary necrotic cells","volume":"581","author":"Zeerleder","year":"2007","journal-title":"FEBS Lett"},{"key":"10.1111\/jth.12094_bb0160","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1165\/rcmb.2010-0158OC","article-title":"CD44 is protective during hyperoxia\u2010induced lung injury","volume":"44","author":"van der Windt","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1111\/jth.12094_bb0165","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1182\/blood-2007-06-096651","article-title":"The ligand occupancy of endothelial protein C receptor switches the protease\u2010activated receptor 1\u2010dependent signaling specificity of thrombin from a permeability\u2010enhancing to a barrier\u2010protective response in endothelial cells","volume":"110","author":"Bae","year":"2007","journal-title":"Blood"},{"key":"10.1111\/jth.12094_bb0170","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1172\/JCI42629","article-title":"Activated protein C targets CD8 + dendritic cells to reduce the mortality of endotoxemia in mice","volume":"120","author":"Kerschen","year":"2010","journal-title":"J Clin Invest"},{"key":"10.1111\/jth.12094_bb0175","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1097\/01.CCM.0000074719.40109.95","article-title":"Elevated nucleosome levels in systemic inflammation and sepsis","volume":"31","author":"Zeerleder","year":"2003","journal-title":"Crit Care Med"},{"key":"10.1111\/jth.12094_bb0180","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1056\/NEJMoa1202290","article-title":"Drotrecogin alfa (activated) in adults with septic shock","volume":"366","author":"Ranieri","year":"2012","journal-title":"N Engl J Med"},{"issue":"Suppl 5","key":"10.1111\/jth.12094_bb0185","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/cc6154","article-title":"Recombinant human activated protein C: current insights into its mechanism of action","volume":"11","author":"Levi","year":"2007","journal-title":"Crit Care"},{"key":"10.1111\/jth.12094_bb0190","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1172\/JCI44266","article-title":"New players in the sepsis\u2010protective activated protein C pathway","volume":"120","author":"Ruf","year":"2010","journal-title":"J Clin Invest"},{"key":"10.1111\/jth.12094_bb0195","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1084\/jem.20070404","article-title":"Endotoxemia and sepsis mortality reduction by non\u2010anticoagulant activated protein C","volume":"204","author":"Kerschen","year":"2007","journal-title":"J Exp Med"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjth.12094","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjth.12094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S153878362211130X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S153878362211130X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/onlinelibrary.wiley.com\/wol1\/doi\/10.1111\/jth.12094\/fullpdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T03:07:12Z","timestamp":1761534432000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S153878362211130X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["S153878362211130X"],"URL":"https:\/\/doi.org\/10.1111\/jth.12094","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2013,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Endogenous protein C has a protective role during Gram\u2010negative pneumosepsis (melioidosis)","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1111\/jth.12094","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2013 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}