Fibrocytes Ameliorate Acute Lung Injury by Decreasing Inflammatory Cytokine and Chemokine Levels and Reducing Neutrophil Accumulation in the Lung

Fibrocytes Ameliorate Acute Lung Injury by Decreasing Inflammatory Cytokine and Chemokine Levels and Reducing Neutrophil Accumulation in the Lung
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纤维细胞通过降低炎症细胞因子和趋化因子水平以及减少肺中中性粒细胞积聚来改善急性肺损伤

DOI:
10.1159/000485647
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发表时间:
2017-12
影响因子:
--
通讯作者:
董昭兴
董昭兴
中科院分区:
医学1区
文献类型:
--
作者:
邰文琳;徐益恒;董昭兴

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背景/目的:急性肺损伤(ALI)在世界范围内仍然是威胁人类生命的严重疾病。为了降低ALI的死亡率,提高ALI的治疗效果,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尚未研究。因此,采用脂多糖(LPS)诱导小鼠ALI模型。方法:从博来霉素小鼠外周血单个核细胞中获取纤维细胞,采用流式细胞术检测分子制造蛋白的表达。采用纤维细胞注射治疗急性肺损伤小鼠。采用ELISA法检测支气管肺泡灌洗液(BALF)上清液中细胞因子(TNF-α、IL-6、IFN-γ)浓度,评价疗效。结果:LPS诱导ALI小鼠体内肿瘤坏死因子-α (TNF-α)、白细胞介素-6 (IL-6)、干扰素-γ (IFN-γ)等细胞因子浓度升高。给药后,TNF-α、IL-6和IFN-γ的浓度以及mRNA和蛋白的表达水平均降低。纤维细胞改善ALI的作用具有时间依赖性。LPS处理诱导髓过氧化物酶(MPO)活性增加,而纤维细胞处理则抑制MPO活性以及中性粒细胞趋化趋化因子巨噬细胞炎症蛋白2 (MIP-2)的表达。结论:综上所述,这些数据表明,纤维细胞通过抑制炎症细胞因子和趋化因子以及减少肺中性粒细胞的积累来改善ALI。
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). Methods: 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. Results: 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). Conclusion: 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.
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