Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis
Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis
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DOI：
10.3858/emm.2010.42.6.048
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发表时间：
2010-06-30
影响因子：
12.8
通讯作者：
Park, Sung Hak
中科院分区：
文献类型：
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作者：
Song, Jeong Sup;Kang, Chun Mi;Park, Sung Hak
CXC趋化因子受体4 （CXCR4）结合基质细胞衍生因子-1 (SDF-1)，已被证明在动员骨髓（BM）来源的干细胞和炎症细胞中发挥关键作用。我们研究了CXCR4拮抗剂AMD3100对博莱霉素诱导的小鼠肺纤维化模型的影响。用AMD3100治疗博来霉素治疗的小鼠，早期支气管肺泡灌洗液（BAL）中SDF-1含量降低，随后肺纤维细胞减少。AMD3100降低了博莱霉素损伤后早期（第3天）肺组织中SDF-1 mRNA的表达和纤维细胞数量，降低了后期（第7天和第21天）CXCR4的表达。在博来霉素损伤后期，AMD3100可明显减轻胶原含量和肺纤维化。在体外用博来霉素处理肺裂解物或SDF-1刺激时，AMD3100处理也降低了小鼠间充质干细胞和造血干细胞的趋化性。在BM干细胞实验中，SDF-1诱导的p38 MAPK磷酸化被AMD3100显著阻断。我们的数据表明，AMD3100可能通过阻断SDF-1/CXCR4轴抑制纤维细胞向受损肺的动员，从而有效预防肺纤维化。
CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor-1 (SDF-1), has been shown to play a critical role in mobilizing the bone marrow (BM)-derived stem cells and inflammatory cells. We studied the effects of AMD3100, CXCR4 antagonist, on a murine bleomycin-induced pulmonary fibrosis model. Treatment of mice with AMD3100 in bleomycin-treated mice resulted in the decrease of SDF-1 in bronchoalveolar lavage (BAL) fluids at an early stage and was followed by the decrease of fibrocytes in the lung. AMD3100 treatment decreased the SDF-1 mRNA expression, fibrocyte numbers in the lung at an early stage (day 3) and CXCR4 expression at the later stage (day 7 and 21) after bleomycin injury. The collagen content and pulmonary fibrosis were significantly attenuated by AMD3100 treatment in later stage of bleomycin injury. AMD3100 treatment also decreased the murine mesenchymal and hematopoietic stem cell chemotaxis when either in the stimulation with bleomycin treated lung lysates or SDF-1 in vitro. In BM stem cell experiments, the phosphorylation of p38 MAPK which was induced by SDF-1 was significantly blocked by addition of AMD3100. Our data suggest that AMD3100 might be effective in preventing the pulmonary fibrosis by inhibiting the fibrocyte mobilization to the injured lung via blocking the SDF-1/CXCR4 axis.