Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Cytotherapy. 2018 Mar;20(3):302-313. doi: 10.1016/j.jcyt.2018.01.003. Epub 2018 Feb 12.
Pneumonia is the fourth leading cause of death worldwide, and Streptococcus pneumoniae is the most commonly associated pathogen. Increasing evidence suggests that mesenchymal stromal cells (MSCs) have anti-inflammatory roles during innate immune responses such as sepsis. However, little is known about the effect of MSCs on pneumococcal pneumonia.
Bone marrow-derived macrophages (BMDMs) were stimulated with various ligands in the presence or absence of MSC-conditioned medium. For in vivo studies, mice intranasally-inoculated with S. pneumoniae were intravenously treated with MSCs or vehicle, and various parameters were assessed.
After stimulation with toll-like receptor (TLR) 2, TLR9 or TLR4 ligands, or live S. pneumoniae, TNF-α and interleukin (IL)-6 levels were significantly decreased, whereas IL-10 was significantly increased in BMDMs cultured in MSC-conditioned medium. In mice, MSC treatment decreased the number of neutrophils in bronchoalveolar lavage fluid (BALF) after pneumococcal infection, and this was associated with a decrease in myeloperoxidase activity in the lungs. Levels of proinflammatory cytokines, including TNF-α, IL-6, GM-CSF and IFN-γ, were significantly lower in MSC-treated mice, and the bacterial load in the lung after pneumococcal infection was significantly reduced. In addition, histopathologic analysis confirmed a decrease in the number of cells recruited to the lungs; however, lung edema, protein leakage into the BALF and levels of the antibacterial protein lipocalin 2 in the BALF were comparable between the groups.
These results indicate that MSCs could represent a potential therapeutic application for the treatment of pneumonia caused by S. pneumoniae.
肺炎是全球第四大致死原因，而肺炎链球菌是最常见的相关病原体。越来越多的证据表明，间充质基质细胞（MSCs）在脓毒症等固有免疫反应中具有抗炎作用。然而，对于 MSCs 对肺炎链球菌性肺炎的影响知之甚少。
骨髓来源的巨噬细胞（BMDMs）在存在或不存在 MSC 条件培养基的情况下用各种配体刺激。在体内研究中，用 S. pneumoniae 鼻内接种的小鼠静脉内用 MSC 或载体处理，并评估各种参数。
在 TLR2、TLR9 或 TLR4 配体或活 S. pneumoniae 刺激后，BMDMs 在 MSC 条件培养基中培养时 TNF-α 和白细胞介素（IL）-6 水平显著降低，而 IL-10 水平显著升高。在小鼠中，MSC 治疗可减少肺炎链球菌感染后支气管肺泡灌洗液（BALF）中的中性粒细胞数量，这与肺部髓过氧化物酶活性的降低有关。促炎细胞因子（包括 TNF-α、IL-6、GM-CSF 和 IFN-γ）的水平在 MSC 治疗的小鼠中显著降低，肺炎链球菌感染后肺部的细菌负荷也显著降低。此外，组织病理学分析证实肺部募集的细胞数量减少；然而，两组间肺水肿、BALF 中蛋白渗漏以及 BALF 中抗菌蛋白 lipocalin 2 的水平相当。
这些结果表明，MSCs 可能代表一种治疗肺炎链球菌引起的肺炎的潜在治疗应用。
