TY -的T1 VEGF-C / VEGFR-3信号在巨噬细胞改善急性肺损伤JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00880 -2021欧元SP - 2100880 AU山下式Masahiro AU - Niisato,鸠山幸AU -川崎,靖盟——Karaman Sinem AU - Robciuc,马吕斯r . AU - Shibata Yuji AU -石田跟非盟-西AU Ryosuke -增田，AU Tomoyuki - Sugai, AU Tamotsu - Ono, AU Masao - Tuder, Rubin M. AU - Alitalo, AU Kari -山内从急性肺损伤中成功恢复需要抑制中性粒细胞内流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。目的探讨巨噬细胞血管内皮生长因子受体-3 (VEGFR-3)/VEGF-C信号转导在脂多糖诱导肺损伤中的改善作用。方法将脂多糖经鼻内注射于野生型小鼠和转基因小鼠体内。VEGF-C/VEGFR-3信号转导功能实验采用腺病毒介导的鼻内输送VEGF-C (Ad-VEGF-C载体)和可溶性VEGFR-3，或抗VEGFR-3阻断抗体和骨髓细胞中VEGFR-3缺失的小鼠。VEGF-C的过表达可明显减轻肺损伤的早期，同时增加支气管肺泡灌洗液(BALF)白介素(IL)-10的水平，而Ad-sVEGFR-3载体抑制后肺损伤的晚期则加重。在小鼠恢复阶段注射抗vegfr -3抗体抑制肺损伤的恢复。VEGFR-3缺失小鼠的生存时间比同窝小鼠短，且在分解阶段肺损伤更严重。在分解期的肺泡巨噬细胞消化了大部分外来的凋亡中性粒细胞，VEGF-C/VEGFR-3信号通过上调巨噬细胞内的整合素α v来增加efferocytosis。 We also found that incubation with BALF from acute respiratory distress syndrome (ARDS) patients, but not from controls, decreases VEGFR-3 expression and the efficiency of IL-10 expression and efferocytosis in human monocyte-derived macrophages.Conclusions VEGFR-3/VEGF-C signaling in macrophages ameliorates experimental lung injury. 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. ER -