{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:12:34Z","timestamp":1791227554080,"version":"4.1.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The involvement of neutrophil activation in the sentinel, potentially reversible, events in the pathogenesis of acute lung injury (ALI) is only partially understood. \u03b1-Defensins are the most abundant proteins secreted by activated human neutrophils, but their contribution to ALI in mouse models is hindered by their absence from murine neutrophils and the inability to study their effects in isolation in other species.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To study the role of \u03b1-defensins in the pathogenesis of ALI in a clinically relevant setting using mice transgenic for polymorphonuclear leukocyte expression of \u03b1-defensins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transgenic mice expressing polymorphonuclear leukocyte \u03b1-defensins were generated. ALI was induced by acid aspiration. Pulmonary vascular permeability was studied in vivo using labeled dextran and fibrin deposition. The role of the low-density lipoprotein\u2013related receptor (LRP) in permeability was examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Acid aspiration induced neutrophil migration and release of \u03b1-defensins into lung parenchyma and airways. ALI was more severe in \u03b1-defensin\u2013expressing mice than in wild-type mice, as determined by inspection, influx of neutrophils into the interstitial space and airways, histological evidence of epithelial injury, interstitial edema, extravascular fibrin deposition, impaired oxygenation, and reduced survival. Within 4 hours of insult, \u03b1-defensin\u2013expressing mice showed greater disruption of capillary\u2013epithelial barrier function and ALI that was attenuated by systemic or intratracheal administration of specific inhibitors of the LRP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\u03b1-Defensins mediate ALI through LRP-mediated loss of capillary\u2013epithelial barrier function, suggesting a potential new approach to intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200907-1128oc","type":"journal-article","created":{"date-parts":[[2010,1,21]],"date-time":"2010-01-21T22:10:52Z","timestamp":1264111852000},"page":"935-946","source":"Crossref","is-referenced-by-count":76,"title":["Neutrophil \u03b1-Defensins Cause Lung Injury by Disrupting the Capillary\u2013Epithelial Barrier"],"prefix":"10.1093","volume":"181","author":[{"given":"Khalil","family":"Bdeir","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abd Al-Roof","family":"Higazi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"},{"name":"Department of Clinical Biochemistry, Hebrew University\u2013Hadassah Medical School, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kulikovskaya","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melpo","family":"Christofidou-Solomidou","sequence":"additional","affiliation":[{"name":"Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei 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