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 -增田良介,AU - Sugai友之,AU - Ono Tamotsu, AU - Tuder Masao, Rubin M. AU - Alitalo, Kari AU - Yamauchi,急性肺损伤的成功恢复需要抑制中性粒细胞内流和清除凋亡的中性粒细胞。然而,复苏背后的机制仍不清楚。目的研究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对巨噬细胞的改善作用。方法野生型和转基因小鼠鼻内注射脂多糖。VEGF-C/VEGFR-3信号功能的获得和丧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阻断抗体和髓系细胞中VEGFR-3缺失的小鼠。结果VEGF-C过表达、BALF白细胞介素(IL)-10水平升高可明显减轻早期肺损伤,Ad-sVEGFR-3载体抑制VEGFR-3可加重晚期肺损伤。在分解期小鼠注射抗vegfr -3抗体可抑制肺损伤的恢复。VEGFR-3缺失的小鼠比同窝的小鼠生存时间短,在解决期肺损伤更严重。肺泡巨噬细胞在分解期消化了大部分外部凋亡的中性粒细胞,而VEGF-C/VEGFR-3信号通路通过上调巨噬细胞内整合素α v而增加了泡沫细胞增多。 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 -