Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells.

Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells.
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DOI:
10.1084/jem.186.6.825
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发表时间:
1997-09-15
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Wells TN
Wells TN
中科院分区:
其他
文献类型:
--
作者:
Power CA;Church DJ;Meyer A;Alouani S;Proudfoot AE;Clark-Lewis I;Sozzani S;Mantovani A;Wells TN

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树突状细胞是参与免疫应答启动的有效抗原呈递细胞。这些细胞向组织和淋巴结的运输由趋化因子家族的成员介导。最近,从EMBL/GenBank/DDBJ表达序列标签数据库中发现了一种新的CC趋化因子MIP-3α(liver and activation-regulated chemokine)。在目前的研究中,我们已经表明MIP-3α的信使RNA主要在炎症和粘膜组织中表达。MIP-3α对CD 34+来源的树突状细胞和T细胞具有趋化性,但对单核细胞和中性粒细胞无活性。MIP-3α不能取代特异性CC或CXC趋化因子与表达其各自高亲和力受体(即CCR 1 -5和CXCR 1和CXCR 2)的稳定细胞系的结合,表明MIP-3α通过一种新型CC趋化因子受体发挥作用。因此,我们使用基于简并寡核苷酸的逆转录酶PCR来鉴定肺树突状细胞中的候选MIP-3α受体。我们的研究结果表明,孤儿受体GCY-4、CKRL-3或STRL-22是MIP-3α的特异性受体,当其在HEK 293细胞中表达时,其激活导致百日咳毒素敏感性和磷脂酶C依赖性细胞内Ca 2+动员。
Dendritic cells are potent antigen-presenting cells involved in the initiation of immune responses. The trafficking of these cells to tissues and lymph nodes is mediated by members of the chemokine family. Recently, a novel CC chemokine known as MIP-3α or liver and activation-regulated chemokine has been identified from the EMBL/GenBank/DDBJ expressed sequence tag database. In the present study, we have shown that the messenger RNA for MIP-3α is expressed predominantly in inflamed and mucosal tissues. MIP-3α produced either synthetically or by human embryonic kidney 293 cells is chemotactic for CD34+-derived dendritic cells and T cells, but is inactive on monocytes and neutrophils. MIP-3α was unable to displace the binding of specific CC or CXC chemokines to stable cell lines expressing their respective high affinity receptors, namely CCR1–5 and CXCR1 and CXCR2, suggesting that MIP-3α acts through a novel CC chemokine receptor. Therefore, we used degenerate oligonucleotide-based reverse transcriptase PCR to identify candidate MIP-3α receptors in lung dendritic cells. Our results show that the orphan receptor known as GCY-4, CKRL-3, or STRL-22 is a specific receptor for MIP-3α, and that its activation leads to pertussis toxin–sensitive and phospholipase C–dependent intracellular Ca2+ mobilization when it is expressed in HEK 293 cells.
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发表时间: 1996-09-01
期刊: The Journal of experimental medicine
影响因子: --
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发表时间: 1991-10-01
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