Nakatsutsumi Keita, Park Dong Jun, Choi Wooil, Johnston William, Pool Katie, Kezios Jenny, Coimbra Raul, Eliceiri Brian P, Costantini Todd W
Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, UC San Diego School of Medicine, 200 West Arbor Drive, San Diego, CA, 92103-8896, USA.
Trauma and Acute Critical Care Center, Institute of Science Tokyo Hospital, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Inflamm Res. 2025 May 24;74(1):83. doi: 10.1007/s00011-025-02051-2.
To evaluate the micro-RNA (miRNA) cargo of alveolar small extracellular vesicles (sEVs) after lung contusion (LC), which can contribute to the development of trauma-related acute lung injury (ALI).
A mouse model of LC was conducted with a controlled cortical impact device. Bronchoalveolar lavage fluid (BAL) was collected 24 h post-injury and sEVs were purified using size exclusion chromatography. sEVs characteristics and miRNA cargo were analyzed with vesicle flow cytometry and sequencing. Macrophages were treated with BAL sEVs in vitro to assess their pro-inflammatory effect.
LC increased lung permeability and caused ALI histologically. LC increased the number of sEVs in the BAL and altered their miRNA cargo. BAL sEVs collected after LC increased pro-inflammatory cytokine release from macrophages.
LC increased the mobilization of sEVs to the alveolar space and modified their miRNA cargo that might contribute to the development of ALI by activating the immune response in macrophages.
评估肺挫伤(LC)后肺泡小细胞外囊泡(sEVs)中的微小RNA(miRNA)含量,其可能促进创伤相关急性肺损伤(ALI)的发展。
使用可控皮质撞击装置建立LC小鼠模型。在损伤后24小时收集支气管肺泡灌洗液(BAL),并使用尺寸排阻色谱法纯化sEVs。用囊泡流式细胞术和测序分析sEVs的特征和miRNA含量。在体外将巨噬细胞用BAL sEVs处理,以评估其促炎作用。
LC增加了肺通透性,并在组织学上导致ALI。LC增加了BAL中sEVs的数量,并改变了其miRNA含量。LC后收集的BAL sEVs增加了巨噬细胞促炎细胞因子的释放。
LC增加了sEVs向肺泡腔的动员,并改变了其miRNA含量,这可能通过激活巨噬细胞中的免疫反应促进ALI的发展。