{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:42:05Z","timestamp":1791110525279,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"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":[[2004,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neutrophil elastase (NE) remains a controversial player in the process of leukocyte transmigration and much of this controversy stems from conflicting reports on the effects of NE inhibitors. The availability of NE-deficient mice (NE\u2212\/\u2212) provides a clean and elegant tool for the study of leukocyte migration in vivo. In this study, NE\u2212\/\u2212 mice were used to investigate the role of NE in leukocyte migration through cremasteric venules, as observed by intravital microscopy, induced by locally administered cytokines IL-1\u03b2 and TNF-\u03b1 and the particulate stimulus, zymosan. Although no defects in leukocyte responses induced by the cytokines were observed, zymosan-induced leukocyte firm adhesion and transmigration was suppressed in NE\u2212\/\u2212 mice. These responses were also inhibited in wild-type mice when zymosan was coinjected with a specific NE inhibitor. Quantification of inflammatory mediator levels in homogenates of zymosan-stimulated tissues indicated reductions in levels of IL-1\u03b2, KC, and macrophage inflammatory protein-1\u03b1 in NE\u2212\/\u2212 mice. Furthermore, phagocytosis of fluorescent zymosan particles, as observed by intravital microscopy, was diminished in NE-deficient animals. Collectively, the findings of this study indicate a nonredundant role for NE in zymosan-induced leukocyte firm adhesion and transmigration, and that this defect is associated with impaired generation of proinflammatory mediators as well as phagocytosis of zymosan particles in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.172.7.4493","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:56:20Z","timestamp":1398030980000},"page":"4493-4502","source":"Crossref","is-referenced-by-count":105,"title":["Neutrophil Elastase (NE)-Deficient Mice Demonstrate a Nonredundant Role for NE in Neutrophil Migration, Generation of Proinflammatory Mediators, and Phagocytosis in Response to Zymosan Particles In Vivo"],"prefix":"10.1093","volume":"172","author":[{"given":"Rebecca E","family":"Young","sequence":"first","affiliation":[{"name":"Cardiovascular Medicine Unit, Eric Bywaters Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D","family":"Thompson","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Unit, Eric Bywaters Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Y","family":"Larbi","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Unit, Eric Bywaters Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mylinh","family":"La","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Bart\u2019s and the London, Queen Mary University of London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare E","family":"Roberts","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Unit, Eric Bywaters Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Perretti","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Bart\u2019s and the London, Queen Mary University of London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sussan","family":"Nourshargh","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Unit, Eric Bywaters Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,4,1]]},"reference":[{"key":"2025032708031681800_R1","first-page":"598","volume-title":"Thromb. 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