Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3
Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3
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DOI：
10.1074/jbc.271.13.7725
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发表时间：
1996-03-29
影响因子：
4.8
通讯作者：
Yoshie, O
中科院分区：
文献类型：
--
作者：
Kitaura, M;Nakajima, T;Yoshie, O
CC 趋化因子嗜酸细胞趋化因子是豚鼠嗜酸性粒细胞的选择性趋化剂，首先从过敏性气道炎症模型的豚鼠支气管肺泡灌洗液中纯化。我们现已分离出嗜酸细胞趋化因子的人类对应物的基因和 cDNA。该基因定位于 17 号染色体，在小肠和结肠中高水平表达，在其他各种组织中低水平表达。推导的成熟蛋白序列与人单核细胞趋化蛋白-1 具有 66% 的同一性，与豚鼠嗜酸细胞趋化因子具有 60% 的同一性。昆虫细胞中产生的重组人嗜酸性粒细胞趋化因子在正常人嗜酸性粒细胞中诱导钙通量反应，但在中性粒细胞或单核细胞中则不然。用其他 CC 趋化因子预处理嗜酸性粒细胞不能使反应脱敏，这表明存在独特的受体。在这方面，我们证明人嗜酸性粒细胞趋化因子是 CC 趋化因子受体 3 的有效且高度特异性的激动剂，CC 趋化因子受体 3 是一种在人嗜酸性粒细胞中选择性表达的 G 蛋白偶联受体。因此，eotaxin 和 CC 趋化因子受体 3 可能是炎症中嗜酸性粒细胞募集高度特化的宿主因子，并且可能是开发用于治疗嗜酸性粒细胞参与发病的炎症性疾病（例如哮喘）的选择性药物的良好靶点。
The CC chemokine eotaxin is a selective chemoattractant for guinea pig eosinophils, first purified from bronchoalveolar lavage fluid in a guinea pig model of allergic airway inflammation. We have now isolated the gene and cDNA for a human counterpart of eotaxin. The gene maps to chromosome 17 and is expressed constitutively at high levels in small intestine and colon, and at lower levels in various other tissues. The deduced mature protein sequence is 66% identical to human monocyte chemoattractant protein-1, and 60% identical to guinea pig eotaxin. Recombinant human eotaxin produced in insect cells induced a calcium flux response in normal human eosinophils, but not in neutrophils or monocytes. The response could not be desensitized by pretreatment of eosinophils with other CC chemokines, suggesting a unique receptor. In this regard, we show that human eotaxin is a potent and highly specific agonist for CC chemokine receptor 3, a G protein-coupled receptor selectively expressed in human eosinophils. Thus eotaxin and CC chemokine receptor 3 may be host factors highly specialized for eosinophil recruitment in inflammation, and may be good targets for the development of selective drugs for inflammatory diseases where eosinophils contribute to pathogenesis, such as asthma.