Signal Relay by CC Chemokine Receptor 2 (CCR2) and Formylpeptide Receptor 2 (Fpr2) in the Recruitment of Monocyte-derived Dendritic Cells in Allergic Airway Inflammation
Signal Relay by CC Chemokine Receptor 2 (CCR2) and Formylpeptide Receptor 2 (Fpr2) in the Recruitment of Monocyte-derived Dendritic Cells in Allergic Airway Inflammation
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DOI：
10.1074/jbc.m113.450635
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发表时间：
2013-06-07
影响因子：
4.8
通讯作者：
Wang, Ji Ming
中科院分区：
文献类型：
--
作者：
Chen, Keqiang;Liu, Mingyong;Wang, Ji Ming
趋化因子受体调节炎症部位的白细胞积聚。在过敏性气道炎症中，尽管趋化因子受体CCR 2参与介导单核细胞衍生的树突细胞（DC）募集到肺中，但我们先前也发现在甲酰肽受体Fpr 2（Fpr 2（-/-））缺陷的小鼠中，DC在发炎肺中的积累减少。因此，我们研究了Fpr 2与CCR 2合作在过敏性气道炎症中单核细胞衍生的DC的运输中的作用。我们报道在过敏性气道炎症中，CCR 2介导单核细胞衍生的DC向血管周围区域的募集，并且Fpr 2是细胞进一步迁移到细支气管区域所必需的。我们还发现，来自患有气道炎症的小鼠的支气管肺泡灌洗液含有CCR 2配体CCL 2和Fpr 2激动剂CRAMP。此外，类似于Fpr 2（-/-）小鼠，在CRAMP（-/-）小鼠的发炎气道中，DC运输到支气管周围区域减少。我们的研究表明CCR 2和Fpr 2与其内源性配体的相互作用依次介导了DCs在炎症肺内的运输。
Chemoattractant receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine receptor CCR2 was implicated in mediating monocyte- derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in formylpeptide receptor Fpr2 (Fpr2(-/-)). We therefore investigated the role of Fpr2 in the trafficking of monocyte- derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte- derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2(-/-) mice, in the inflamed airway of CRAMP(-/-) mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung.