Potential Role of DARC-Chemokine Interaction in the Recruitment of Osteoclast Precursors in Response to Bacterial Lipopolysaccharide Challenge.
Potential Role of DARC-Chemokine Interaction in the Recruitment of Osteoclast Precursors in Response to Bacterial Lipopolysaccharide Challenge.
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DOI：
10.1007/s00223-016-0170-2
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发表时间：
2016-11
影响因子：
4.2
通讯作者：
Edderkaoui, Bouchra
中科院分区：
文献类型：
--
作者：
Alemi, Fatemeh;Elgendy, Mohamed;Edderkaoui, Bouchra
达菲抗原趋化因子受体（DARC）与许多促炎趋化因子结合，由于已知趋化因子可调节破骨细胞（OC）前体的运输，我们预测DARC将通过调节趋化因子活性来调节OC向炎症部位的募集。为了验证这一假设，我们在细菌脂多糖（LPS）处理的内皮细胞中评估了Darc的mRNA表达和已知与Darc结合的趋化因子。LPS处理后内皮细胞中Mcp-1、Rantes、Darc和Ccr5 mRNA表达显著升高。用中和抗体阻断DARC的功能可以部分消除LPS对Mcp-1和Rantes mRNA表达的影响。在体内，使用靶向破坏Darc基因的小鼠（Darc- ko）和对照野生型小鼠（WT）来评估Darc在顶骨顶部单次LPS作用下的作用。注射lps 5小时后，两系小鼠的Cd14 mRNA（炎症单核细胞的标志物）的局部表达均显著增加。然而，与DARC - ko小鼠相比，WT小鼠的增加幅度更大，这表明DARC在LPS反应中介导单核细胞的募集中发挥了作用。从注射部位的颅骨切片中进行的抗酒石酸酸性磷酸酶（TRAP）的组织学染色显示，与WT小鼠相比，Darc-KO小鼠对LPS的反应显著减少了每骨表面的TRAP标记表面。基于这些发现，我们得出结论，DARC调节炎症部位OC前体的募集，可能是通过调节趋化因子跨内皮细胞屏障的胞饮作用。
Duffy antigen receptor for chemokines (DARC) binds to a number of pro-inflammatory chemokines, and since chemokines are known to regulate trafficking of osteoclast (OC) precursors, we predicted that DARC would regulate OC recruitment to sites of inflammation by modulating chemokine activity. To test this hypothesis, we evaluated the mRNA expression of Darc and the chemokines known to bind to DARC, in endothelial cells treated with bacterial lipopolysaccharide (LPS). The mRNA expression of Mcp-1, Rantes, Darc and Ccr5 was significantly increased in endothelial cells in response to LPS treatment. Blocking the function of DARC with neutralizing antibody partially abrogated the effect of LPS on the mRNA expression of Mcp-1 and Rantes. In vivo, mice with targeted disruption of Darc gene (Darc-KO) and control wild type (WT) mice were used to assess the role of DARC in response to single LPS application on the top of parietal bones. Five hours post-LPS injection, local expression of Cd14 mRNA (a marker of inflammatory monocytes) was significantly increased in both lines of mice. However, the magnitude of increase was greater in WT mice compared to Darc-KO mice suggesting a role for DARC in mediating the recruitment of monocytes in response to LPS. Histological staining for tartrate-resistant acid phosphatase (TRAP) in calvaria sections taken from the injection sites revealed a significant reduction in TRAP-labeled surface per bone surface in response to LPS in Darc-KO mice compared to WT mice. Based on these findings, we concluded that DARC regulates recruitment of OC precursors at the inflammation site, probably through regulation of chemokines transcytosis across endothelial cell barrier.
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影响因子：
3.7
作者：
Rundle CH;Mohan S;Edderkaoui B
通讯作者：
Edderkaoui B
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56.9
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3.1
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30.5
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作者：
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通讯作者：
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