{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:30:54Z","timestamp":1786595454506,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03dx11k66","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001661","name":"Heidelberg University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001661","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Early detection of acute lung injury (ALI) remains challenging, as conventional diagnostics rarely capture initial molecular changes. We therefore examined whether extracellular vesicles (EVs) in bronchoalveolar lavage fluid (BALF) can detect early regional injury and distinguish initial stress mechanisms in a porcine ALI model. Unilateral ALI was induced using Triton X-100, followed by six hours of mechanical ventilation with either fixed positive end-expiratory pressure (PEEP) at 5 cmH2O or transpulmonary-pressure (TPP)-guided PEEP. Spatially separated BALF sampling allowed direct comparison between injured and contralateral mechanically stressed lungs. EV concentration and size distribution were quantified by nano-flow cytometry, while vesicular identity was confirmed by transmission electron microscopy and tetraspanin dot blot analyses. Furthermore, EV metrics were related to corresponding histologic injury scores. Across both PEEP strategies, EV concentration was markedly higher in both directly injured and contralateral mechanically stressed lungs compared with sham controls, indicating alveolar stress beyond the primary injury site. Median EV size differed significantly by injury type and correlated inversely with histologic injury, particularly with alveolar neutrophil infiltration. BALF-derived EV concentration and size may therefore provide complementary, spatially resolved molecular readouts of early ALI.<\/jats:p>","DOI":"10.3390\/ijms27167173","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:32:16Z","timestamp":1786444336000},"page":"7173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles from Bronchoalveolar Lavage Fluid Indicate Early Biomarker Potential and Differentiate Local Lung Injury in a Porcine Model of Asymmetric Acute Lung Injury"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6110-2713","authenticated-orcid":false,"given":"Benjamin","family":"Seybold","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Medical Faculty, University Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7762-4597","authenticated-orcid":false,"given":"Anna Lena","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute for Lung Research, Universities of Giesen and Marburg Lung Center, German Center for Lung Research (DZL), Philipps-University Marburg, 35043 Marburg, Germany"},{"name":"Core Facility Flow Cytometry\u2013Bacterial Vesicles, Philipps-University Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Feuerbach","sequence":"additional","affiliation":[{"name":"Institute for Lung Research, Universities of Giesen and Marburg Lung Center, German Center for Lung Research (DZL), Philipps-University Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Heimerl","sequence":"additional","affiliation":[{"name":"Center for Synthetic Microbiology (SYNMIKRO), Philipps-University Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine H.","family":"Mutschler","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Medical Faculty, University Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Englert","sequence":"additional","affiliation":[{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University Heidelberg, 69120 Heidelberg, Germany"},{"name":"Institute of Pathology, Heidelberg University Hospital, Medical Faculty, University Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleo-Aron","family":"Weis","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, Medical Faculty, University Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Poth","sequence":"additional","affiliation":[{"name":"Center for Model System and Comparative Pathology (CMCP), Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Medical Faculty, University Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Kalenka","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Medical Faculty, University Heidelberg, 69120 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University Heidelberg, 69120 Heidelberg, Germany"},{"name":"District Hospital Bergstrasse, 69646 Heppenheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-2783","authenticated-orcid":false,"given":"Mascha O.","family":"Fiedler-Kalenka","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Medical Faculty, University Heidelberg, 69120 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. 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