{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T02:50:01Z","timestamp":1768013401897,"version":"3.49.0"},"reference-count":47,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/501100001697","name":"Keio University","doi-asserted-by":"publisher","award":["Grant-in-Aid for Encouragement of Young Medical Scientists"],"award-info":[{"award-number":["Grant-in-Aid for Encouragement of Young Medical Scientists"]}],"id":[{"id":"10.13039\/501100001697","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","award":["18H02821"],"award-info":[{"award-number":["18H02821"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","award":["18K19566"],"award-info":[{"award-number":["18K19566"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:p> Pulmonary emphysema is a major manifestation of chronic obstructive pulmonary disease and is associated with chronic pulmonary inflammation caused by cigarette smoking, with contributions from immune cells such as neutrophils, macrophages, and lymphocytes. Although matrix metalloproteinases are well known to contribute to emphysema progression, the role of a disintegrin and metalloproteinase (ADAM) family proteins, other major metalloproteinases, in disease pathogenesis is largely unknown. ADAM17 is a major sheddase that cleaves various cell surface proteins, including CD62L, an adhesion molecule that plays a critical role in promoting the migration of immune cells to the site of inflammation. In the present study, we aimed to investigate the potential role of ADAM17 and CD62L in the development of elastase-induced emphysema. Control and Adam17<jats:sup>flox\/flox<\/jats:sup>\/Mx1-Cre ( Adam17<jats:sup>\u0394Mx1<\/jats:sup>) mice (8\u201310 wk old) were intratracheally injected with 5 units of porcine pancreas elastase and monitored for 35 days after injection. Lung alveolar destruction was evaluated by analyzing the mean linear intercepts of lung tissue specimens and by histopathological examination. Mean linear intercepts data indicated that the degree of elastase-induced emphysema was significantly more severe in Adam17<jats:sup>\u0394Mx1<\/jats:sup> mice. Furthermore, flow cytometry showed that CD62L<jats:sup>+<\/jats:sup> neutrophil, CD62L<jats:sup>+<\/jats:sup> macrophage, and CD62L<jats:sup>+<\/jats:sup> B lymphocyte numbers were significantly increased in Adam17<jats:sup>\u0394Mx1<\/jats:sup> mice. Moreover, the pharmacological depletion of CD62L<jats:sup>+<\/jats:sup> cells with a CD62L-neutralizing antibody ameliorated the extent of emphysema in Adam17<jats:sup>\u0394Mx1<\/jats:sup> mice. Collectively, these results suggest that ADAM17 possibly suppresses the progression of emphysema by proteolytically processing CD62L in immune cells and that ADAM17 and CD62L could be novel therapeutic targets for treating pulmonary emphysema. <\/jats:p>","DOI":"10.1152\/ajplung.00214.2019","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T19:09:36Z","timestamp":1583348976000},"page":"L1172-L1182","source":"Crossref","is-referenced-by-count":10,"title":["ADAM17 protects against elastase-induced emphysema by suppressing CD62L<sup>+<\/sup> leukocyte infiltration in mice"],"prefix":"10.1152","volume":"318","author":[{"given":"Shoji","family":"Suzuki","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan"},{"name":"Japan Society of Promotion of Science, Tokyo, 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