{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:49:26Z","timestamp":1793386166286,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Federal Ministry of Education and Research","award":["01KI07110 (Giessen)"],"award-info":[{"award-number":["01KI07110 (Giessen)"]}]},{"name":"German Federal Ministry of Education and Research","award":["01KI07111 (Jena)"],"award-info":[{"award-number":["01KI07111 (Jena)"]}]},{"name":"German Federal Ministry of Education and Research","award":["01KI07113 (Leipzig)"],"award-info":[{"award-number":["01KI07113 (Leipzig)"]}]},{"name":"German Federal Ministry of Education and Research","award":["01KI07114 (Berlin)"],"award-info":[{"award-number":["01KI07114 (Berlin)"]}]},{"name":"German Federal Ministry of Education and Research","award":["01KI1010I (Leipzig)"],"award-info":[{"award-number":["01KI1010I (Leipzig)"]}]},{"name":"German Federal Ministry of Education and Research","award":["01KI1010D (Greifswald)"],"award-info":[{"award-number":["01KI1010D (Greifswald)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>During pneumonia, pathogen\u2013host interaction evokes inflammation and lung barrier dysfunction. Tie2 activation by angiopoietin-1 reduces, whereas Tie2 blockade by angiopoietin-2 increases, inflammation and permeability during sepsis. The role of angiopoietin-1\/-2 in pneumonia remains unidentified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the prognostic and pathogenic impact of angiopoietins in regulating pulmonary vascular barrier function and inflammation in bacterial pneumonia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum angiopoietin levels were quantified in pneumonia patients of two independent cohorts (n\u2009=\u2009148, n\u2009=\u2009395). Human postmortem lung tissue, pneumolysin- or angiopoietin-2\u2013stimulated endothelial cells, isolated perfused and ventilated mouse lungs, and mice with pneumococcal pneumonia were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In patients with pneumonia, decreased serum angiopoietin-1 and increased angiopoietin-2 levels were observed as compared with healthy subjects. Higher angiopoietin-2 serum levels were found in patients with community-acquired pneumonia who died within 28 days of diagnosis compared with survivors. Receiver operating characteristic analysis revealed improved prognostic accuracy of CURB-65 for 28-day survival, intensive care treatment, and length of hospital stay if combined with angiopoietin-2 serum levels. In vitro, pneumolysin enhanced endothelial angiopoietin-2 release, angiopoietin-2 increased endothelial permeability, and angiopoietin-1 reduced pneumolysin-evoked endothelial permeability. Ventilated and perfused lungs of mice with angiopoietin-2 knockdown showed reduced permeability on pneumolysin stimulation. Increased pulmonary angiopoietin-2 and reduced angiopoietin-1 mRNA expression were observed in Streptococcus pneumoniae\u2013infected mice. Finally, angiopoietin-1 therapy reduced inflammation and permeability in murine pneumonia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data suggest a central role of angiopoietin-1\/-2 in pneumonia-evoked inflammation and permeability. Increased angiopoietin-2 serum levels predicted mortality and length of hospital stay, and angiopoietin-1 may provide a therapeutic target for severe pneumonia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201708-1733oc","type":"journal-article","created":{"date-parts":[[2018,2,15]],"date-time":"2018-02-15T18:08:32Z","timestamp":1518718112000},"page":"220-231","source":"Crossref","is-referenced-by-count":76,"title":["Prognostic and Pathogenic Role of Angiopoietin-1 and -2 in Pneumonia"],"prefix":"10.1093","volume":"198","author":[{"given":"Birgitt","family":"Gutbier","sequence":"first","affiliation":[{"name":"Division of Pulmonary Inflammation and"},{"name":"Department of Infectious Diseases and Pulmonary Medicine, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Kathrin","family":"Neuhau\u00df","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Pulmonary Medicine, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Reppe","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Inflammation and"},{"name":"Department of Infectious Diseases and Pulmonary Medicine, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Ehrler","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Pulmonary Medicine, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar","family":"Santel","sequence":"additional","affiliation":[{"name":"Silence Therapeutics AG, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Silence Therapeutics AG, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Scholz","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Weissmann","sequence":"additional","affiliation":[{"name":"Excellence Cluster 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hippenstiel","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Pulmonary Medicine, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Suttorp","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Pulmonary Medicine, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"CAPNETZ STIFTUNG, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Witzenrath","sequence":"additional","affiliation":[{"name":"Division of Pulmonary 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