RT期刊文章SR电子T1的负面角色肥大细胞在慢性阻塞性肺病chymase-1摩根富林明欧洲呼吸杂志乔和J FD欧元欧洲呼吸学会SP 2101431 10.1183/13993003.01431 -2021签证官60是6 A1帮刘A1安德鲁·g·Jarnicki A188bet官网地址1 Keshav r . Paudel A1署名为陆A1 Ridhima Wadhwa A1 Ashleigh m . Philp A1 Hannelore Van Eeckhoutte A1杰奎琳·e·马歇尔A1 Vamshikrishna Malyla A1当归Katsifis A1 A1妮可·g·迈克尔•弗里克Hansbro A1 Kamal Dua A1 Nazanin z Kermani A1马修s Eapen A1当归Tiotiu A1 K。粉丝涌A1盖太诺Caramori A1马克肯A1伊恩·m·爱德考克A1 Sukhwinder s Sohal A1彼得·a·华克A1布莱恩·g·奥利弗A1菲利普·m·Hansbro年2022 UL //www.qdcxjkg.com/content/60/6/2101431.abstract AB背景慢性阻塞性肺病是全世界第三大死因。香烟(CS)全身的慢性炎症诱导气道重构,肺气肿和肺功能受损的主要原因。迫切需要有效的治疗方法。人类chymase (hCMA) 1及其orthologue mCMA1 /鼠标肥大细胞蛋白酶(mMCP) 5从激活肥大细胞胞吐,在许多疾病产生不良作用,但他们的角色在慢性阻塞性肺病是未知的。方法评估hCMA1水平在慢性阻塞性肺病患者的肺组织。我们使用mmcp5-deficient(−−)老鼠来评估这个蛋白酶的作用和潜在的治疗目标CS-induced实验性慢性阻塞性肺病。此外,我们使用体外/体外研究定义机制。结果hCMA1 mRNA水平和CMA1 +肺组织中肥大细胞增加严重/轻度慢性阻塞性肺病患者早期相比,non-COPD吸烟者和健康对照组。脱粒肥大细胞数量和mMCP5蛋白质增加野生型小鼠实验性慢性阻塞性肺病的肺组织。/ mmcp5−−老鼠防止CS-induced炎症和巨噬细胞积累,气道重塑、肺气肿和肺功能受损在实验性慢性阻塞性肺病。 CS extract challenge of co-cultures of mast cells from wild-type, but not mmcp5−/− mice with wild-type lung macrophages increased in tumour necrosis factor (TNF)-α release. It also caused the release of CMA1 from human mast cells, and recombinant hCMA-1 induced TNF-α release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD.Conclusion CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-α expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD.hCMA1 released from mast cells induces macrophages to release TNF-α in the lung and promotes the pathogenesis of COPD. hCMA1 may be a novel therapeutic target in COPD. https://bit.ly/3b3OkKT