Ty-jour t1 - 骨髓细胞特异性诱导的一氧化氮合酶缺失免受小鼠的烟雾诱导的肺动脉高压 - 欧洲呼吸期刊jo - 欧元jo - eur reshir J do - 10.1183 / 13993003 - 2101153-2021 SP - 2101153 Au - Gredic，Marija Au- 吴，程宇奥地克，斯特凡·奥 - ·帕克，Oleg Au - Savai，Rajkumar Au - Kojonazarov，Baktybek Au - Doswada，Siddartha Au - Weiss，Astrid Au - Weigert，Antreas Au - Gu - Guenther，Andreas Au - Brandes，RALF P. Au - Schermuly，Ralpht T. Au - Grimminger，Friidrich Au - Seeger，Werner Au - Sommer，Natascha Au - Kraut，Simone Au - Weissmann，Norbert Y1 - 2021/01/01/01/01/01/01/01/01/01/01/01/01/01 / 01/01/01ersjournals.com/content/early/2021/07/29/13993003.01153-2021.bstract n2 - 肺动脉高压（pH）是慢性阻塞性肺病（COPD）的常见并发症，与增加的死亡率和发病率相关。有趣的是，已经提出了肺血管改变来驱使肺气肿的发展。以前鉴定了诱导的一氧化氮合酶（InOS）作为烟草诱导的pH和肺气肿的发育和逆转的必要酶，并显示骨髓衍生细胞中的InOS表达驱动肺血管重塑，但不予实质破坏。在这项研究中，我们旨在鉴定探测烟雾诱导的pH的Inos表达的细胞类型并涉及的促进促进途径。在慢性烟雾暴露中解决我们使用的这个问题1）骨髓细胞特异性Inos淘汰小鼠，2）巨噬细胞和肺动脉平滑肌细胞（PASMC）的共同培养物译成底层信号通路.MYLOID细胞特异性INOS敲除防止烟雾诱导的pH但不是小鼠肺气肿。此外，在骨髓细胞中缺失缺失改善了CD206表达的增加，在间质巨噬细胞上的CD206的表达式。重要的是，观察到对肺巨噬细胞的影响缺氧无关，因为这些小鼠产生了缺氧诱导的pH值。 In vitro, smoke-induced PASMC proliferation in co-cultures with M2-polarised macrophages could be abolished by iNOS deletion in phagocytic cells, as well as by ERK inhibition in PASMC. Crucially, CD206-positive and iNOS-positive macrophages accumulated in proximity of remodelled vessels in the lungs of COPD patients, as shown by immunohistochemistry.In summary, our results demonstrate that iNOS deletion in myeloid cells confers protection against PH in smoke-exposed mice and provide evidence for an iNOS-dependent communication between M2-like macrophages and PASMC in underlying pulmonary vascular remodelling.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. 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 -