ADAM17 protects against elastase-induced emphysema by suppressing CD62L+ leukocyte infiltration in mice

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. Eight-to-ten-week-old control and Adam17flox/flox/Mx1-Cre (Adam17ΔMx1) mice were intratracheally injected with 5 U of porcine pancreas elastase and monitored for 3...

肺气肿（Pulmonary emphysema）是慢性阻塞性肺疾病（chronic obstructive pulmonary disease）的主要临床表现，与吸烟诱发的慢性肺部炎症相关，中性粒细胞、巨噬细胞及淋巴细胞等免疫细胞参与该炎症过程。尽管基质金属蛋白酶（matrix metalloproteinases）在肺气肿进展中的促发作用已广为人知，但另一类核心金属蛋白酶——解整合素金属蛋白酶（a disintegrin and metalloproteinase, ADAM）家族蛋白在该病发病机制中的作用仍尚未明确。ADAM17作为一类主要的脱落酶（sheddase），可剪切CD62L等多种细胞表面蛋白；CD62L作为黏附分子，在促进免疫细胞向炎症部位迁移的过程中发挥关键作用。本研究旨在探究ADAM17与CD62L在弹性蛋白酶诱导的肺气肿发生发展中的潜在作用。选取8~10周龄的对照组小鼠与Adam17flox/flox/Mx1-Cre（Adam17ΔMx1）小鼠，经气管内注射5单位猪胰腺弹性蛋白酶，并开展为期3……的监测。