{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T04:36:01Z","timestamp":1789878961723,"version":"4.0.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Urokinase receptor (urokinase-type plasminogen activator receptor [uPAR], CD87), a GPI-anchored protein, is considered to play an important role in inflammation and fibrinolysis. The Gram-negative bacterium Burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in Southeast Asia. In this study, we investigated the expression and function of uPAR both in patients with septic melioidosis and in a murine model of experimental melioidosis. uPAR mRNA and surface expression was increased in patients with septic melioidosis in\/on both peripheral blood monocytes and granulocytes as well as in the pulmonary compartment during experimental pneumonia-derived melioidosis in mice. uPAR-deficient mice intranasally infected with B. pseudomallei showed an enhanced growth and dissemination of B. pseudomallei when compared with wild-type mice, corresponding with increased pulmonary and hepatic inflammation. uPAR knockout mice demonstrated significantly reduced neutrophil migration toward the pulmonary compartment after inoculation with B. pseudomallei. Further in vitro experiments showed that uPAR-deficient macrophages and granulocytes display a markedly impaired phagocytosis of B. pseudomallei. Additional studies showed that uPAR deficiency did not influence hemostatic and fibrinolytic responses during severe melioidosis. These data suggest that uPAR is crucially involved in the host defense against sepsis caused by B. pseudomallei by facilitating the migration of neutrophils toward the primary site of infection and subsequently facilitating the phagocytosis of B. pseudomallei.<\/jats:p>","DOI":"10.4049\/jimmunol.0901008","type":"journal-article","created":{"date-parts":[[2010,2,8]],"date-time":"2010-02-08T20:44:50Z","timestamp":1265661890000},"page":"3079-3086","source":"Crossref","is-referenced-by-count":48,"title":["Urokinase Receptor Is Necessary for Bacterial Defense against Pneumonia-Derived Septic Melioidosis by Facilitating Phagocytosis"],"prefix":"10.1093","volume":"184","author":[{"given":"W Joost","family":"Wiersinga","sequence":"first","affiliation":[{"name":"Center for Infection and Immunity Amsterdam"},{"name":"Center for Experimental and Molecular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth M","family":"Kager","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity Amsterdam"},{"name":"Center for Experimental and Molecular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joppe W R","family":"Hovius","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity Amsterdam"},{"name":"Center for Experimental and Molecular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerritje J W","family":"van der Windt","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity Amsterdam"},{"name":"Center for Experimental and Molecular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex F","family":"de Vos","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity Amsterdam"},{"name":"Center for Experimental and Molecular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost C M","family":"Meijers","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris J","family":"Roelofs","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, University of Amsterdam , Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen","family":"Dondorp","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Levi","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P","family":"Day","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok,","place":["Thailand"]},{"name":"Center for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford , Oxford,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J","family":"Peacock","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok,","place":["Thailand"]},{"name":"Center for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford , Oxford,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"van der Poll","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity Amsterdam"},{"name":"Center for Experimental and Molecular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,3,15]]},"reference":[{"key":"2026012806264049700_r1","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nrm977","article-title":"uPAR: a versatile signalling orchestrator.","volume":"3","author":"Blasi","year":"2002","journal-title":"Nat. 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