Identification of granulocyte subtype-selective receptors and ion channels by using a high-density oligonucleotide probe array
Identification of granulocyte subtype-selective receptors and ion channels by using a high-density oligonucleotide probe array
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DOI：
10.1016/j.jaci.2003.12.036
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发表时间：
2004-03-01
影响因子：
14.2
通讯作者：
Saito, H
中科院分区：
文献类型：
--
作者：
Nakajima, T;Iikura, M;Saito, H
背景：在炎症过程中，中性粒细胞、嗜碱性粒细胞和嗜酸性粒细胞通过信号分子（如G蛋白偶联受体和离子通道）释放细胞类型特异性介质和蛋白酶。因此，离子通道和受体，包括G蛋白偶联受体，是常见的药物靶点。目的：我们首次试图确定每种粒细胞亚型优先表达的离子通道和受体。方法：使用GeneChip，我们比较了7种白细胞类型、血小板、肥大细胞和成纤维细胞中大约20,000个转录本，以鉴定受体和离子通道的粒细胞亚型选择性转录本。粒细胞亚型选择性转录本的选择基于几个条件，例如转录本的表达水平比其他白细胞的最高水平高5倍或更高。结果：51个转录本在不同的粒细胞亚型中优先表达。51个转录本中有17个先前未报道为粒细胞亚型选择性。在17个受体和离子通道中，有6个是嗜碱性粒细胞选择性、嗜酸性粒细胞选择性或两者兼有，且在其他器官中不高表达，提示它们可能是抗过敏药物的潜在靶点。结论：使用这个潜在的细胞类型选择性药物靶点数据库可以最大限度地减少药物开发所需的工作量。
Background: During inflammation, neutrophils, basophils, and eosinophils release cell type-specific mediators and proteases through signaling molecules, such as G protein-coupled receptors and ion channels. As such, ion channels and receptors, including G protein-coupled receptors, are common drug targets.Objective: We sought to identify, for the first time, ion channels and receptors preferentially expressed by each granulocyte subtype.Methods: Using GeneChip, we compared approximately 20,000 transcripts present in 7 leukocyte types, platelets, mast cells, and fibroblasts to identify granulocyte subtype-selective transcripts for receptors and ion channels. Granulocyte subtype-selective transcripts were chosen on the basis of several conditions, such as the transcript having a 5-fold or greater expression level compared with the maximum level of other leukocytes.Results: Fifty-one transcripts were chosen to be preferentially expressed by each granulocyte subtype. Seventeen of the 51 transcripts have not been previously reported as granulocyte subtype selective. Among the 17 receptors and ion channels, 6 were basophil selective, eosinophil selective, or both and were not highly expressed by other organs, indicating that they might be potential targets for antiallergy drugs.Conclusion: Use of this database of potential cell type-selective drug targets should minimize the efforts required for pharmaceutical development.