{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:18:47Z","timestamp":1788153527194,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020027","name":"Dr. Rolf M. Schwiete Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neutrophil extracellular traps (NETs) are chromatin-based structures released by activated neutrophils that are associated with microvascular thrombosis and pulmonary inflammation. These are adverse effects that are relevant in ECMO-associated lung injury. Although enzymatic NET degradation by DNase1 represents a potential anti-inflammatory strategy, its anti-inflammatory effects in the lung tissue and on vascular endothelial growth factor (VEGF) signalling have received limited investigation. We used a tissue-architecture\u2013preserving murine lung explant model to characterise inflammation following exposure to activated neutrophils and to determine whether DNase1 attenuates this response without compromising VEGF expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Murine lung tissue in an explant culture was exposed to phorbol 12-myristate 13-acetate\u2013activated human neutrophils. DNase1 was used to prevent NET-mediated effects. Inflammatory and angiogenic responses were assessed using multiplex proximity extension assay and quantitative immunofluorescence of peribronchiolar regions of interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In whole-explant lysates, the pre-specified primary analyte C-C motif chemokine ligand 5 (Ccl5) was significantly increased following exposure to activated neutrophils (p = 0.015); among exploratory analytes, C-C motif chemokine ligand 3 remained significant after false-discovery-rate correction (Ccl3 p = 0.005, q = 0.014), while C-X-C motif chemokine ligand 9 was nominally elevated (Cxcl9 p = 0.041, q = 0.061). Immunofluorescence confirmed increased Ccl5, in the peribronchiolar regions (p = 0.002, q = 0.004), which was significantly attenuated by DNase1 (p = 0.019, q = 0.038). Vascular endothelial growth factor expression was not significantly altered by neutrophil exposure or DNase1 treatment (p \u2265 0.29).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      NET-associated inflammation in murine lung explants is detected within peribronchiolar regions of interest and is attenuated by DNase1-mediated degradation of extracellular DNA without compromising VEGF expression. These findings provide a rationale for further evaluating DNase1 as a candidate adjunct anti-inflammatory strategy in ECMO-associated lung injury, where the preservation of VEGF expression alongside NET inhibition is potentially attractive given the bleeding risks of conventional anticoagulation. Clinical applicability requires confirmation in flow-based ex vivo systems,\n                      <jats:italic>in vivo<\/jats:italic>\n                      models, and human ECMO studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1883328","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:29:14Z","timestamp":1788150554000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["DNase1 reverses peribronchial inflammation in murine explants incubated with activated neutrophils"],"prefix":"10.3389","volume":"17","author":[{"given":"Hong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]},{"name":"European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg 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Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Boettcher","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]},{"name":"European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]},{"name":"Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Martel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]},{"name":"European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, 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