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.
The study was aimed to explore the functions of circulating fibrocytes (CFs) on injury repair in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) mice model and its clinical value as a biomarker for ALI/ARDS. ALI/ARDS mice model was established by intratracheal instillation of lipopolysaccharide (LPS). Mononuclear cells were isolated from peripheral blood of ALI/ARDS model and flow cytometry was used to measure CFs defined as cells positive for CD45 and collagen-1. Histological changes of lung tissues were evaluated by H&E staining and Masson's trichrome staining. The correlations of CFs counts with damnification of lung tissue and the severity of pulmonary fibrosis were evaluated by Pearson correlation analyses. Western blot was used to detect the protein expression of collagen-1. ELISA was applied to determine cytokine CXCL12 concentration. Clinical relevance between CFs and ALI/ARDS was investigated. The greater number of CFs in the ALI/ARDS group implied higher degree of lung injury and more severe pulmonary fibrosis. The protein expression of collagen-1 and concentration of cytokine CXCL12 in ALI/ARDS group were higher than that in control group. Clinical and prognostic analysis revealed the higher injury degree and death rates in ALI/ARDS group than those in control group, and identified a greater severity and mortality for patients with ARDS than those with ALI. ROC curve analysis indicated the counts of CFs greater than 5.85% can predict death rates with AUC = 0.928. CFs had an inhibitory effect on injury repair in ALI/ARDS mice model. This might be unfavorable as a clinical marker for progression of ALI/ARDS.
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