Cloning and Characterization of a Specific Receptor for the Novel CC Chemokine MIP-3α from Lung Dendritic Cells

作者：Christopher Power, Dennis J. Church, Alexandra Meyer, Sami Alouani, Amanda E. I. Proudfoot, Ian Clark‐Lewis, Silvano Sozzani, Alberto Mantovani, Timothy N. C. Wells · 发表于：The Journal of Experimental Medicine · 年份：1997 · DOI：10.1084/jem.186.6.825 · 被引用次数：290 · 研究领域：Chemokine receptors and signaling、Immunotherapy and Immune Responses、T-cell and B-cell Immunology

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.