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Abstract：
OBJECTIVE: 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).
CONCLUSIONS: 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.
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).
CONCLUSIONS: 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.
摘要：
目的：急性肺损伤（ALI）仍然是威胁全世界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,用脂多糖（LPS）诱导小鼠ALI模型。
方法：从博莱霉素小鼠外周血单个核细胞中收集成纤维细胞，并通过流式细胞术检测分子标记物的表达。将纤维细胞注射用于治疗急性肺损伤小鼠。用ELISA法测定细胞因子(包括TNF-α,支气管肺泡灌洗液（BALF）上清液中的IL-6和IFN-γ）浓度。
结果：细胞因子的浓度，如肿瘤坏死因子-α（TNF-α），白细胞介素-6（IL-6），在LPS诱导的ALI小鼠中，干扰素-γ（IFN-γ）增加。TNF-α的浓度,IL-6和IFN-γ以及它们的mRNA和蛋白质表达水平通过施用纤维细胞而降低。纤维细胞改善ALI的作用是时间依赖性的。LPS处理诱导髓过氧化物酶（MPO）活性增加，而纤维细胞处理导致MPO活性抑制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。
结论：综合来看，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中嗜中性粒细胞的积累来改善ALI.
方法：从博莱霉素小鼠外周血单个核细胞中收集成纤维细胞，并通过流式细胞术检测分子标记物的表达。将纤维细胞注射用于治疗急性肺损伤小鼠。用ELISA法测定细胞因子(包括TNF-α,支气管肺泡灌洗液（BALF）上清液中的IL-6和IFN-γ）浓度。
结果：细胞因子的浓度，如肿瘤坏死因子-α（TNF-α），白细胞介素-6（IL-6），在LPS诱导的ALI小鼠中，干扰素-γ（IFN-γ）增加。TNF-α的浓度,IL-6和IFN-γ以及它们的mRNA和蛋白质表达水平通过施用纤维细胞而降低。纤维细胞改善ALI的作用是时间依赖性的。LPS处理诱导髓过氧化物酶（MPO）活性增加，而纤维细胞处理导致MPO活性抑制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。
结论：综合来看，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中嗜中性粒细胞的积累来改善ALI.
