Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran.
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran.
Int Immunopharmacol. 2020 Mar;80:105879. doi: 10.1016/j.intimp.2019.105879. Epub 2019 Nov 22.
Sulfur Mustard (SM) is one of the most lethal chemicals with major complications manifested in the lungs. Although the pathogenesis behind SM-induced lung injury still remains poorly understood, prolonged activation and the imbalance of two major macrophage populations (M1 and M2) have been suggested to be involved. Here, we tried to investigate the effectiveness of adipose-derived mesenchymal stem cells (AD-MSC) on long-term lesions induced by CEES, an SM analog. The modulation of pulmonary immune cells and alveolar macrophage phenotype alteration was studied in the animal model used.
Histopathological changes were investigated in the lungs and analysis of surface markers of alveolar macrophages as well as their cytokine expression in the BAL fluid was carried out by flow cytometry and ELISA, respectively.
Treatment of mice with AD-MSC after intraperitoneal administration of CEES (10 mg/kg) reduces progressive histopathologic changes in the lung. Flow cytometric analysis of isolated alveolar macrophages in the bronchoalveolar lavage showed that the accumulation of both M1 and M2 macrophages in response to CEES was reduced by MSC administration. AD-MSCs caused a marked reduction in the CD86- and CD206-expressing macrophages compared to the untreated groups. The modulating effect of AD-MSCs in the M1-subset was much more significant compared to M2. These findings suggest that AD-MSCs understand their environment and restore the balance in disorders associated with Th1 or Th2 imbalance. Our results indicate that MSCs may represent an effective approach to repair lung injury induced by mustards.
硫芥（SM）是最致命的化学物质之一，主要并发症表现在肺部。尽管 SM 诱导的肺损伤的发病机制仍不清楚，但长时间的激活和两种主要巨噬细胞群体（M1 和 M2）的失衡已被认为与之相关。在这里，我们试图研究脂肪间充质干细胞（AD-MSC）对 CEES 诱导的长期肺损伤的治疗效果，CEES 是一种 SM 类似物。在使用的动物模型中研究了肺免疫细胞的调节和肺泡巨噬细胞表型改变。
通过流式细胞术和 ELISA 分别研究肺部的组织病理学变化以及肺泡巨噬细胞表面标志物和 BAL 液中细胞因子的表达。
CEES（10mg/kg）腹腔给药后，AD-MSC 治疗可减轻小鼠肺部进行性组织病理学改变。对支气管肺泡灌洗液中分离的肺泡巨噬细胞进行流式细胞术分析表明，MSC 给药可减少 CEES 引起的 M1 和 M2 巨噬细胞的积聚。与未治疗组相比，AD-MSCs 导致 CD86 和 CD206 表达的巨噬细胞明显减少。AD-MSCs 对 M1 亚群的调节作用比 M2 更为显著。这些发现表明，AD-MSCs 可以理解其环境，并在与 Th1 或 Th2 失衡相关的疾病中恢复平衡。我们的结果表明，MSC 可能是修复芥子气诱导的肺损伤的有效方法。
