Tai Wenlin, Xu Yiheng, Ding Jiawei, Wu Hanxin, Du Ming, Qu Xiaoyuan, Gao Ling, Li Jinyu, Dong Zhaoxing
Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second affiliated hospital of Kunming Medical University, Kunming, China.
Department of Respiration, The Sencond Affiliated Hospital of Kunming Medical University, Kunming, China.
Cell Physiol Biochem. 2017;44(4):1526-1536. doi: 10.1159/000485647. Epub 2017 Dec 4.
BACKGROUND/AIMS: Acute lung injury (ALI) remains a severe disease that threatens human life around the world. To decrease the mortality of ALI and improve ALI treatment efficacy, the development of more ALI treatments is urgently needed. Whether fibrocytes directly participate in ALI has not been studied. Therefore, a mouse model of ALI was induced with lipopolysaccharide (LPS).
Fibrocytes were harvested from peripheral blood mononuclear cells of bleomycin mice and identified by using flow cytometry to detect the expression of molecular makers. The fibrocytes were injected for the treatment of acute lung injury mice. The curative effects were evaluated by using ELISA to determine the cytokines (including TNF-α, IL-6 and IFN-γ) concentrations in bronchoalveolar lavage fluid (BALF) supernatant.
The concentrations of cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ) were increased in mice with ALI induced with LPS. The concentrations of TNF-α, IL-6, and IFN-γ as well as their mRNA and protein expression levels were decreased by administration of fibrocytes. The effect of fibrocytes in ameliorating ALI was time dependent. LPS treatment induced an increase in myeloperoxidase (MPO) activity, whereas the fibrocyte treatment caused inhibition of MPO activity as well as expression of the neutrophil-chemoattractant chemokine macrophage inflammatory protein 2 (MIP-2).
Taken together, these data suggest that fibrocytes ameliorated ALI by suppressing inflammatory cytokines and chemokines as well as by decreasing the accumulation of neutrophils in the lung.
背景/目的:急性肺损伤(ALI)仍然是一种严重威胁全球人类生命的疾病。为降低ALI的死亡率并提高其治疗效果,迫切需要开发更多的ALI治疗方法。纤维细胞是否直接参与ALI尚未得到研究。因此,用脂多糖(LPS)诱导建立了ALI小鼠模型。
从博来霉素小鼠的外周血单个核细胞中分离收获纤维细胞,并通过流式细胞术检测分子标志物的表达进行鉴定。将纤维细胞注射用于治疗急性肺损伤小鼠。通过酶联免疫吸附测定(ELISA)法测定支气管肺泡灌洗液(BALF)上清液中细胞因子(包括肿瘤坏死因子-α、白细胞介素-6和干扰素-γ)的浓度来评估治疗效果。
用LPS诱导的ALI小鼠中,肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和干扰素-γ(IFN-γ)等细胞因子的浓度升高。给予纤维细胞后,TNF-α、IL-6和IFN-γ的浓度及其mRNA和蛋白表达水平均降低。纤维细胞改善ALI的作用具有时间依赖性。LPS处理导致髓过氧化物酶(MPO)活性增加,而纤维细胞处理则抑制了MPO活性以及中性粒细胞趋化因子巨噬细胞炎性蛋白2(MIP-2)的表达。
综上所述,这些数据表明纤维细胞通过抑制炎性细胞因子和趋化因子以及减少肺内中性粒细胞的积聚来改善ALI。