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The A Disintegrin and Metalloproteinase 17 (ADAM17) regulates inflammatory signaling through ectodomain shedding of adhesion molecules and cytokine receptors, yet its endothelial-specific contribution to acute lung injury remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Endothelial ADAM17 was deleted in ADAM17\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      Tie2-Cre\n                      <jats:sup>+<\/jats:sup>\n                      mice using the Cre\/loxP system. Acute lung inflammation was induced by lipopolysaccharide (LPS) inhalation. Systemic ADAM17 blockade was achieved by intraperitoneal TAPI\u20111 or ADAM17\/ADAM10 inhibition by GW280264X, administered 1\u00a0h before LPS. Pulmonary microvascular permeability was quantified by Evans Blue extravasation. Neutrophil trafficking across lung compartments (intravascular, endothelial adherent, interstitial, intra\u2011alveolar) was assessed by flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Endothelial ADAM17 emerged as a central regulator of vascular permeability, neutrophil trafficking, and inflammatory amplification in LPS-induced acute pulmonary inflammation. LPS markedly increased pulmonary ADAM17 expression, whereas endothelial-specific deletion reduced total lung ADAM17 mRNA by 77.5%, highlighting the dominant endothelial contribution. Endothelial ADAM17 deficiency preserved endothelial junction integrity through maintenance of JAM-A surface expression and was associated with preserved expression of VE-cadherin and the tight junction proteins ZO-1, occludin, and claudin-5, thereby reducing protein-rich pulmonary edema. These changes were accompanied by enhanced neutrophil transmigration into interstitial and alveolar compartments through altered PSGL-1 and CD49d expression. Mechanistically, endothelial ADAM17 enhanced TNF receptor 1 and IL-6 receptor signaling, elevating TNF-\u03b1, myeloperoxidase, and neutrophil elastase levels. Pharmacological ADAM17 inhibition recapitulated the protective phenotype of endothelial ADAM17 deficiency, attenuating neutrophil recruitment, preserving endothelial barrier integrity, and limiting vascular leakage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings strengthen the evidence that endothelial ADAM17 is a key driver of inflammatory vascular dysfunction in ARDS and support ADAM17 as a\u00a0rational\u00a0therapeutic\u00a0target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-026-01290-7","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T07:13:31Z","timestamp":1790579611000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial ADAM17 facilitates neutrophil migration and pulmonary microvascular permeability in acute lung inflammation"],"prefix":"10.1186","volume":"33","author":[{"given":"Anna","family":"Biedritzky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Kleinmaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Fuhr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Maria","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian-Christos","family":"Ngamsri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Konrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Koeppen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"12","key":"1290_CR1","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1007\/s00134-011-2380-4","volume":"37","author":"J Villar","year":"2011","unstructured":"Villar J, Blanco J, Anon JM, Santos-Bouza A, Blanch L, Ambros A, et al. 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