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This study aimed to determine if plasma EVs could be manipulated to reduce lung injury. We hypothesized that inhibition of multidrug resistance-associated protein (MRP) 1 on EVs would increase total leukotriene (LT) B\n                      <jats:sub>4<\/jats:sub>\n                      and lipoxin (LX) A\n                      <jats:sub>4<\/jats:sub>\n                      levels and, when incubated with immune cells, would increase bacterial phagocytosis and decrease cytokines secreted by the cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma EVs released from ex vivo perfused human lungs injured with\n                      <jats:italic>E.coli<\/jats:italic>\n                      bacteria (\n                      <jats:italic>E.coli<\/jats:italic>\n                      EV) or from control lungs (nEV) were incubated with LPS and Reversan, a MRP1 inhibitor, and the effect of EVs on bacterial phagocytosis and inflammation was studied using a macrophage cell line. In addition, the therapeutic effects of Reversan were studied in perfused human lungs injured with\n                      <jats:italic>E.coli<\/jats:italic>\n                      pneumonia. Levels of LTB\n                      <jats:sub>4<\/jats:sub>\n                      and LXA\n                      <jats:sub>4<\/jats:sub>\n                      were lower in\n                      <jats:italic>E.coli<\/jats:italic>\n                      EVs compared to nEVs.\n                      <jats:italic>E.coli<\/jats:italic>\n                      EVs were less capable than nEVs to stimulate bacterial phagocytosis by macrophages in vitro. Pretreatment of\n                      <jats:italic>E.coli<\/jats:italic>\n                      EVs with LPS and Reversan increased both total LTB\n                      <jats:sub>4<\/jats:sub>\n                      and LXA\n                      <jats:sub>4<\/jats:sub>\n                      levels, and, when incubated with Raw264.7 cells, bacterial phagocytosis was increased and TNF\u03b1 levels secretion was decreased by the cells. Intravenous administration of Reversan to human lungs injured with\n                      <jats:italic>E.coli<\/jats:italic>\n                      bacterial pneumonia significantly restored alveolar fluid clearance rate and reduced bacterial levels in the injured alveolus at 6\u00a0h.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Administration of a MRP1 inhibitor to plasma EVs increased its LTB\n                      <jats:sub>4<\/jats:sub>\n                      content, which, when incubated with macrophages, further increased phagocytosis of bacteria by the cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40635-026-00902-8","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:53:44Z","timestamp":1777445624000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential role of extracellular vesicles in bacterial phagocytosis during Escherichia coli pneumonia in ex vivo perfused human lungs"],"prefix":"10.1186","volume":"14","author":[{"given":"Hongli","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Sugita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wonjung","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshifumi","family":"Naito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandip","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Matthay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9236-9960","authenticated-orcid":false,"given":"Jae-Woo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"902_CR1","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1056\/NEJMra1608077","volume":"377","author":"BT Thompson","year":"2017","unstructured":"Thompson BT, Chambers RC, Liu KD (2017) Acute respiratory distress syndrome. 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Blood 121:510\u2013518","journal-title":"Blood"}],"container-title":["Intensive Care Medicine Experimental"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40635-026-00902-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40635-026-00902-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40635-026-00902-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:10:13Z","timestamp":1777450213000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40635-026-00902-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["902"],"URL":"https:\/\/doi.org\/10.1186\/s40635-026-00902-8","relation":{},"ISSN":["2197-425X"],"issn-type":[{"value":"2197-425X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"assertion":[{"value":"24 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"We obtained de-identified human donor lungs from the Northern Transplant Donor Network (San Ramon, CA) and One Legacy Transplantation Donor Network (Azusa, CA) not used for clinical transplantation. Because the donors are from deceased individuals, the research lungs are not considered human subject research and does not require a separate IRB approval. UCLA and UCSF IRB approval has been obtained for the collection of human blood from healthy donors for the perfusion of human lungs as well as for the isolation of monocytes and neutrophils for in vitro experiments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/A.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None declared.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"56"}}