TY - T1的骨髓特异性删除诱导一氧化氮合酶防止烟雾诱发小鼠的肺动脉高压JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.01153 -2021欧元SP - 2101153 AU Gredic Marija盟——吴,程毓AU -哈季奇,Stefan AU - Pak,奥列格盟——岛上,拉库马盟——Kojonazarov Baktybek盟——Doswada Siddartha AU -维斯,阿斯特丽德盟——Weigert Andreas AU -德安德烈亚斯盟——Brandes拉尔夫p . AU - Schermuly,拉尔夫·t . AU - Grimminger弗里德里希AU -西格,Werner盟——萨默Natascha盟——德国人,西蒙AU -韦斯曼Norbert Y1 - 2021/01/01 UR - //www.qdcxjkg.com/content/early/2021/07/29/13993003.01153 - 2021. -抽象N2 -肺动脉高压(PH)是一种常见的并发症的慢性阻塞性肺疾病(COPD),相关的死亡率和发病率增加。有趣的是,肺血管已经提出改变驱动肺气肿开发。我们以前确定诱导一氧化氮合酶(间接宾语)作为发展和逆转的关键酶的烟雾诱发PH和肺气肿,从骨髓细胞和显示伊诺表达驱动器肺血管重塑,但没有实质的破坏。在这项研究中,我们旨在识别iNOS-expressing细胞类型驾驶烟雾诱发PH值和破译的前导途径参与。为了解决这个问题我们使用1)骨髓特异性伊诺基因敲除小鼠慢性烟雾暴露,2)共培养的巨噬细胞和肺动脉平滑肌细胞(PASMC)解释潜在的信号通路。髓系特异性伊诺淘汰赛阻止烟雾诱发PH值而不是小鼠肺气肿。此外,伊诺删除髓细胞改善CD206的表达增加,M2两极分化的一个标志,在间质巨噬细胞。重要的是,观察影响肺巨噬细胞hypoxia-independent,这些小鼠低氧诱导博士开发体外,烟雾诱发PASMC增殖与M2-polarised巨噬细胞共培养可以废除伊诺删除的吞噬细胞,以及通过ERK PASMC的抑制。至关重要的是,CD206-positive和iNOS-positive巨噬细胞堆积在邻近改建船舶在COPD患者的肺,通过免疫组织化学方法如图所示。总之,我们的结果表明,伊诺删除在smoke-exposed小鼠骨髓细胞赋予保护PH值和提供证据iNOS-dependent M2-like巨噬细胞之间的通信和PASMC基础肺血管重塑。FootnotesThis手稿最近发表在《欧洲呼吸杂志》上。这里发表周全之前接受的形式排版,我们的生产团队。 After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Gredic has nothing to disclose.Conflict of interest: Dr. Wu has nothing to disclose.Conflict of interest: Dr. Hadzic has nothing to disclose.Conflict of interest: Dr. Pak has nothing to disclose.Conflict of interest: Dr. Savai has nothing to disclose.Conflict of interest: Dr. Kojonazarov has nothing to disclose.Conflict of interest: Dr. Doswada has nothing to disclose.Conflict of interest: Dr. Weiss has nothing to disclose.Conflict of interest: Dr. Weigert has nothing to disclose.Conflict of interest: Dr. Günther has nothing to disclose.Conflict of interest: Dr. Brandes has nothing to disclose.Conflict of interest: Dr. Schermuly has nothing to disclose.Conflict of interest: Dr. Grimminger has nothing to disclose.Conflict of interest: Dr. Seeger reports personal fees from Actelion, personal fees from Bayer AG, personal fees from Novartis, personal fees from Vectura, personal fees from Medspray, personal fees from United Therapeutics, outside the submitted work; .Conflict of interest: Dr. Sommer reports personal fees from Actelion, outside the submitted work; .Conflict of interest: Dr. Kraut has nothing to disclose.Conflict of interest: Dr. Weissmann reports grants from German Research Foundation, during the conduct of the study; In addition, Dr. Weissmann has a patent L-NIL as inhibitor for regenerating the lung of a patient suffering from COPD ER -