{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:22:27Z","timestamp":1789428147306,"version":"build-2803163510"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":37,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL169974"],"award-info":[{"award-number":["R01HL169974"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI135128"],"award-info":[{"award-number":["R01AI135128"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000888","name":"W. M. Keck Foundation","doi-asserted-by":"crossref","award":["994413"],"award-info":[{"award-number":["994413"]}],"id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["K25AI175668"],"award-info":[{"award-number":["K25AI175668"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,22]]},"abstract":"<jats:p>\n                    Invasive aspergillosis is characterized by lung hemorrhage and release of extracellular heme, which promotes fungal growth. Heme can also mediate tissue injury directly, and both fungal growth and lung injury may induce hemorrhage. To assimilate these interdependent processes, we hypothesized that, during aspergillosis, heme mediates direct lung injury independent of fungal growth, leading to worse infection outcomes, and the scavenger protein hemopexin mitigates these effects. Mice with neutropenic aspergillosis developed a time-dependent increase in lung extracellular heme and a corresponding hemopexin induction. Hemopexin deficiency resulted in markedly increased lung injury, fungal growth, and lung hemorrhage. Using a computational model of the interactions of\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    , heme, and the host, we predicted a critical role for heme-mediated generation of neutrophil extracellular traps (NETs) in this infection. We tested this prediction using a fungal strain unable to grow at body temperature and found that extracellular heme and fungal exposure synergized to induce lung injury by promoting NET release, and disruption of NET was sufficient to attenuate lung injury and fungal burden. These data implicate heme-mediated NETosis in both lung injury and fungal growth during aspergillosis, resulting in a detrimental positive feedback cycle that can be interrupted by scavenging heme or disrupting NETs.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.189151","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T12:00:37Z","timestamp":1744718437000},"source":"Crossref","is-referenced-by-count":6,"title":["The heme scavenger hemopexin protects against lung injury during aspergillosis by mitigating release of neutrophil extracellular traps"],"prefix":"10.1172","volume":"10","author":[{"given":"Ganlin","family":"Qu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique A.L.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica L.","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Sordo Vieira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Goddard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nickolas G.","family":"Diodati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa V.","family":"Lazarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Laubenbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-065X","authenticated-orcid":true,"given":"Borna","family":"Mehrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2027424"},{"key":"B2","unstructured":"WHO. WHO fungal priority pathogens list to guide research, development and public health action. https:\/\/www.who.int\/publications\/i\/item\/9789240060241 Updated October 5, 2022. Accessed April 15, 2024"},{"issue":"1","key":"B3","first-page":"115","article-title":"Pulmonary cavitation and massive hemoptysis in invasive pulmonary aspergillosis. Influence of bone marrow recovery in patients with acute leukemia","volume":"131","author":"Albelda","year":"1985","journal-title":"Am Rev Respir Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.3.7663787"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac079"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.318780"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01323"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s12918-016-0275-2"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2021.0806"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00074-22"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.39.1.55.66"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2987"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-529982"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202250011"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201129"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201406-1086OC"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.8.4731-4740.2004"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3RU0620-375R"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.98178"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100239"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.4A0119-009RR"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-019-0139-3"},{"key":"B23"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1309\/UJRV9DLC11RM3G8R"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118885"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000487"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2303077120"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00415"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-11-451229"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89741"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2014.09.007"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/13.6.1151"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-020-01067-x"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060815-014214"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2306318120"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137468"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.105"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000873"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01182"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501811"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2010.06.009"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2019.11.002"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-844530"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.953195"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12700"},{"key":"B46","first-page":"147","article-title":"Quantitative analysis of hemin-induced neutrophil extracellular trap formation and effects of hydrogen peroxide on this phenomenon","volume":"11","author":"Ohbuchi","year":"2017","journal-title":"Biochem Biophys Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaw0336"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1211601"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab188"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2024287118"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s11538-016-0225-6"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00097-12"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002064"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600306"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-020-00176-0"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0210ST"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00194.2013"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/189151\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:39:56Z","timestamp":1779125996000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/189151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,15]]},"references-count":58,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,4,15]]},"published-print":{"date-parts":[[2025,5,22]]}},"alternative-id":["10.1172\/jci.insight.189151"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.189151","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,15]]},"article-number":"e189151"}}