%0杂志文章%A山下，正弘%A Niisato, Miyuki %A川崎，Yasushi %A Karaman, Sinem %A Robciuc, Marius R. %A柴田，石田裕治%A石田裕治，西尾洋治%A Masuda，增田良介%A Sugai, Tamotsu %A Ono, Masao %A Tuder, Rubin M. %A Alitalo, Kari %A Yamauchi，巨噬细胞中的VEGF-C/VEGFR-3信号通路改善急性肺损伤J欧洲呼吸杂志基本原理急性肺损伤的成功恢复需要抑制中性粒细胞流入和清除凋亡中性粒细胞。然而，经济复苏背后的机制仍不清楚。目的研究巨噬细胞血管内皮生长因子受体-3 (VEGFR-3)/VEGF-C信号通路在脂多糖诱导的肺损伤中的改善作用。方法将脂多糖经鼻注射野生型小鼠和转基因小鼠。VEGF-C/VEGFR-3信号功能的获得和损失实验采用腺病毒介导的VEGF-C (Ad-VEGF-C载体)和可溶性VEGFR-3或抗VEGFR-3阻断抗体鼻内传递，以及骨髓细胞中VEGFR-3缺失的小鼠。VEGF-C的过表达和支气管肺泡灌洗液(BALF)白介素(IL)-10水平的升高显著缓解了肺损伤的早期，但Ad-sVEGFR-3载体抑制了VEGFR-3后，肺损伤在晚期加重。在消退期注射抗vegfr -3抗体抑制了肺损伤的恢复。VEGFR-3缺失小鼠的生存时间比同窝小鼠短，在消退期肺损伤更严重。肺泡巨噬细胞在消退期消化了大部分外源性凋亡中性粒细胞，VEGF-C/VEGFR-3信号通路通过上调巨噬细胞内整合素α v增加泡泡细胞作用。我们还发现，急性呼吸窘迫综合征(ARDS)患者的BALF孵育(而不是对照组的BALF孵育)降低了VEGFR-3的表达以及人单核细胞来源的巨噬细胞中IL-10表达和泡沫化的效率。结论巨噬细胞VEGFR-3/VEGF-C信号通路可改善实验性肺损伤。 This mechanism may provide an explanation also for ARDS resolution.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. Yamashita has nothing to disclose.Conflict of interest: Dr. Niisato has nothing to disclose.Conflict of interest: Dr. Kawasaki has nothing to disclose.Conflict of interest: Dr. Karaman has nothing to disclose.Conflict of interest: Dr. Robciuc has nothing to disclose.Conflict of interest: Dr. Shibata has nothing to disclose.Conflict of interest: Dr. Ishida has nothing to disclose.Conflict of interest: Dr. Nishio has nothing to disclose.Conflict of interest: Dr. Masuda has nothing to disclose.Conflict of interest: Dr. Sugai has nothing to disclose.Conflict of interest: Dr. Ono has nothing to disclose.Conflict of interest: Dr. Tuder has nothing to disclose.Conflict of interest: Dr. Alitalo has nothing to disclose.Conflict of interest: Dr. Yamauchi has nothing to disclose. %U //www.qdcxjkg.com/content/erj/early/2021/08/19/13993003.00880-2021.full.pdf