MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF A NOVEL CC-CHEMOKINE RECEPTOR CDNA FROM A HUMAN BASOPHILIC CELL-LINE

MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF A NOVEL CC-CHEMOKINE RECEPTOR CDNA FROM A HUMAN BASOPHILIC CELL-LINE
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DOI:
10.1074/jbc.270.33.19495
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发表时间:
1995-08-18
影响因子:
4.8
通讯作者:
WELLS, TNC
WELLS, TNC
中科院分区:
生物学2区
文献类型:
--
作者:
POWER, CA;MEYER, A;WELLS, TNC

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我们从人未成熟嗜碱性细胞系KU-812中克隆并鉴定了一个新的嗜碱性粒细胞趋化因子受体K5-5。预测的K5-5蛋白序列与巨噬细胞炎性蛋白-1α/RANTES受体(CC CKR-1)的同源性仅为49%,与单核细胞趋化蛋白-1受体(b型)的同源性为47%,表明该基因编码CC趋化因子受体家族的一个新成员。对K5-5mRNA表达的分析表明,K5-5mRNA的表达仅限于白细胞丰富的组织,此外,我们还发现人嗜碱性粒细胞中K5-5mRNA的表达水平显著升高,经白细胞介素5处理后,K5-5mRNA表达上调。CC趋化因子、巨噬细胞炎性蛋白-1α、RANTES和单核细胞趋化蛋白-1能够刺激注射R5-5CRNA的非洲爪哇卵母细胞钙激活的氯离子通道,而对单核细胞趋化蛋白-2、巨噬细胞炎性蛋白-1β和CXC趋化因子IL-8无反应。综上所述,这些结果首次表明嗜碱性粒细胞上存在CC趋化因子受体,该受体的功能与嗜碱性粒细胞介导的过敏性疾病的发病机制有关。
We report the cloning and characterization of a novel basophil CC chemokine receptor, K5-5, from the human immature basophilic cell line KU-812. The predicted protein sequence of K5-5 shows only 49% identity to the macrophage inflammatory protein-1 alpha/RANTES receptor (CC CKR-1) and 47% identity to monocyte chemotactic protein-1 receptor (b form), suggesting that this cDNA encodes a novel member of the CC chemokine receptor family. Analysis of K5-5 mRNA expression indicates that it is restricted to leukocyte-rich tissues, In addition, we have shown significant levels of K5-5 mRNA in human basophils, which were up-regulated by treatment with interleukin-5. The CC chemokines, macrophage inflammatory protein-1 alpha, RANTES, and monocyte chemotactic protein-1 were able to stimulate a Ca2+-activated chloride channel in Xenopus laevis oocytes injected with R5-5 cRNA, whereas no signal was detected in response to monocyte chemotactic protein-2, macrophage inflammatory protein-1 beta, or the CXC chemokine, interleukin-8. Taken together, these results indicate for the first time the presence of a CC chemokine receptor on basophils, which functions as a ''shared'' CC chemokine receptor and may therefore be implicated in the pathogenesis of basophil-mediated allergic diseases.