Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils.

Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils.
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DOI:
10.1038/emm.2013.48
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发表时间:
2013-06-14
影响因子:
12.8
通讯作者:
Bae, Yoe-Sik
Bae, Yoe-Sik
中科院分区:
医学2区
文献类型:
--
作者:
Jung, Young Su;Lee, Ha Young;Kim, Sang Doo;Park, Joon Seong;Kim, Jung Kuk;Suh, Pann-Ghill;Bae, Yoe-Sik

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Wnt5a是一种激活非典型Wnt信号通路(β-catenin-independent pathways)的配体。人类中性粒细胞表达几种Wnt5a受体,如frizzled2、5和8。用Wnt5a刺激人中性粒细胞引起趋化迁移和两种重要趋化因子CXCL8和CCL2的产生。Wnt5a产生CCL2是通过百日咳毒素敏感的g蛋白依赖途径介导的。Wnt5a还刺激了三种丝裂原活化蛋白激酶(MAPK: ERK、p38 MAPK和JNK)和Akt的磷酸化。特异性抑制剂抑制ERK、p38 MAPK或JNK诱导wnt5a诱导的CCL2产生显著减少。脂多糖刺激的巨噬细胞收集的上清液诱导中性粒细胞趋化,抗wnt5a抗体显著抑制。我们的研究结果表明,Wnt5a可能有助于中性粒细胞募集,介导炎症反应。
Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (β-catenin-independent pathways). Human neutrophils expressed several Wnt5a receptors, such as Frizzled 2, 5 and 8. Stimulation of human neutrophils with Wnt5a caused chemotactic migration and the production of two important chemokines, CXCL8 and CCL2. CCL2 production by Wnt5a was mediated by a pertussis toxin-sensitive G-protein-dependent pathway. Wnt5a also stimulated the phosphorylation of three mitogen-activated protein kinases (MAPKs: ERK, p38 MAPK and JNK) and Akt. Inhibition of ERK, p38 MAPK or JNK by specific inhibitors induced a dramatic reduction in Wnt5a-induced CCL2 production. Supernatant collected from lipopolysaccharide-stimulated macrophages induced neutrophil chemotaxis, which was significantly inhibited by anti-Wnt5a antibody. Our results suggested that Wnt5a may contribute to neutrophil recruitment, mediating the inflammation response.
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