{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:01:03Z","timestamp":1774461663038,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T00:00:00Z","timestamp":1395187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["Ta434\/2-1"],"award-info":[{"award-number":["Ta434\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["SFB\/TRR57"],"award-info":[{"award-number":["SFB\/TRR57"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Acute liver failure (<jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>) is a life\u2010threatening condition with a high mortality rate. The expression of urokinase plasminogen activator receptor (uPAR, CD87) and release of its shedded receptor into serum as soluble uPAR (suPAR) have been closely related to immune activation and prognosis in systemic inflammation and cirrhosis. We now aimed at investigating the clinical relevance and cellular source of uPAR and circulating suPAR in ALF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum suPAR concentrations were measured in 48 ALF patients and 62 healthy controls from a German liver transplantation centre. Hepatic immune cell subsets and uPAR expression were studied by FACS, qPCR and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Circulating suPAR levels were significantly increased in ALF patients, independent from the underlying aetiology, in comparison to controls. Serum suPAR concentrations were closely correlated with parameters reflecting liver cell injury, decreased liver function and the model of end\u2010stage liver disease (<jats:styled-content style=\"fixed-case\">MELD<\/jats:styled-content>) score in<jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>patients. By immunohistochemistry from explanted livers,<jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>was associated with distinct immune cell accumulation and strong up\u2010regulation of intrahepatic uPAR mRNA expression. CD87 (uPAR) expression was specifically detected on intrahepatic \u2018non\u2010classical\u2019 monocytes (CD14<jats:sup>+<\/jats:sup>CD16<jats:sup>+<\/jats:sup>), NKT and CD56<jats:sup>dim<\/jats:sup>NK cells isolated from human liver, but not on parenchymal or other non\u2010parenchymal hepatic cell types. Membrane\u2010bound uPAR was rapidly cleaved from monocytes upon inflammatory stimulation by lipopolysaccharide (LPS) and partially by co\u2010cultured lymphocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Similar to its prognostic properties in patients with sepsis or cirrhosis, intrahepatic uPAR activation and serum suPAR concentrations might serve as an interesting biomarker in ALF.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12512","type":"journal-article","created":{"date-parts":[[2014,2,28]],"date-time":"2014-02-28T07:04:24Z","timestamp":1393571064000},"page":"1330-1339","source":"Crossref","is-referenced-by-count":48,"title":["Clinical relevance and cellular source of elevated soluble urokinase plasminogen activator receptor (su<scp>PAR<\/scp>) in acute liver failure"],"prefix":"10.1111","volume":"34","author":[{"given":"Alexander","family":"Koch","sequence":"first","affiliation":[{"name":"Department of Medicine III RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning W.","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Medicine III RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaus","family":"Gassler","sequence":"additional","affiliation":[{"name":"Institute of Pathology RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Jochum","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Bruensing","sequence":"additional","affiliation":[{"name":"Department of Medicine III RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Buendgens","sequence":"additional","affiliation":[{"name":"Department of Medicine III RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"D\u00fcckers","sequence":"additional","affiliation":[{"name":"Department of Medicine III RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Bruns","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II Jena University Hospital Friedrich Schiller University Jena Jena Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Gerken","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf P.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Surgery RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Adams","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Unit and Centre for Liver Research School of Immunity and Infection University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Trautwein","sequence":"additional","affiliation":[{"name":"Department of Medicine III RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Canbay","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Tacke","sequence":"additional","affiliation":[{"name":"Department of Medicine III RWTH\u2010University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60274-7"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00340"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20703"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.06.006"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00056"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00079"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-012-2613-1"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc10037"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm977"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2821"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/504294"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/j.1478-3231.2011.02665.x","article-title":"Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and aetiology of cirrhosis and predicts prognosis","volume":"32","author":"Zimmermann HW","year":"2011","journal-title":"Liver Int"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12054"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.029"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021381"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011049"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.10.020"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26016"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc7925"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.02.016"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199908)180:2<225::AID-JCP10>3.0.CO;2-2"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01488206"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc11434"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.150398"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01624-0"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22104"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25657"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2011.04.016"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.11.027"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2424"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1334485"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2411"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-13-58"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12512","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12512","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.12512","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T17:46:30Z","timestamp":1716572790000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.12512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,19]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1111\/liv.12512"],"URL":"https:\/\/doi.org\/10.1111\/liv.12512","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,19]]}}}