Power C A, Church D J, Meyer A, Alouani S, Proudfoot A E, Clark-Lewis I, Sozzani S, Mantovani A, Wells T N
Geneva Biomedical Research Institute, GlaxoWellcome Research and Development, Geneva, Switzerland.
J Exp Med. 1997 Sep 15;186(6):825-35. doi: 10.1084/jem.186.6.825.
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-3alpha 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-3alpha is expressed predominantly in inflamed and mucosal tissues. MIP-3alpha 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-3alpha 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-3alpha acts through a novel CC chemokine receptor. Therefore, we used degenerate oligonucleotide-based reverse transcriptase PCR to identify candidate MIP-3alpha 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-3alpha, and that its activation leads to pertussis toxin-sensitive and phospholipase C-dependent intracellular Ca2+ mobilization when it is expressed in HEK 293 cells.
树突状细胞是参与免疫反应启动的高效抗原呈递细胞。这些细胞向组织和淋巴结的迁移由趋化因子家族成员介导。最近，从EMBL/GenBank/DDBJ表达序列标签数据库中鉴定出一种名为MIP-3α或肝脏与激活调节趋化因子的新型CC趋化因子。在本研究中，我们已表明MIP-3α的信使核糖核酸主要在炎症组织和粘膜组织中表达。由人胚胎肾293细胞合成产生或其产生的MIP-3α对CD34(+)衍生的树突状细胞和T细胞具有趋化作用，但对单核细胞和中性粒细胞无活性。MIP-3α无法取代特异性CC或CXC趋化因子与表达其各自高亲和力受体（即CCR1-5以及CXCR1和CXCR2）的稳定细胞系的结合，这表明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。我们的结果表明，名为GCY-4、CKRL-3或STRL-22的孤儿受体是MIP-3α的特异性受体，并且当它在HEK 293细胞中表达时，其激活会导致百日咳毒素敏感且依赖磷脂酶C的细胞内Ca2+动员。
