Cloning of the human eosinophil chemoattractant, eotaxin - Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils
Cloning of the human eosinophil chemoattractant, eotaxin - Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils
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DOI：
10.1172/jci118456
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发表时间：
1996-02-01
影响因子：
15.9
通讯作者：
Mackay, CR
中科院分区：
文献类型：
--
作者：
Ponath, PD;Qin, SX;Mackay, CR
在豚鼠和最近在小鼠中发现的CC趋化因子eotaxin可能是嗜酸性粒细胞选择性募集到某些炎症组织的关键因素。利用小鼠eotaxin部分cDNA探针克隆了人eotaxin基因，发现豚鼠和小鼠的eotaxin在氨基酸水平上相同61.8%和63.2%。人eotaxin蛋白在体外是一种强效、特异的嗜酸性粒细胞趋化剂，注射恒河猴皮肤后对嗜酸性粒细胞趋化效果良好。放射标记eotaxin用于鉴定嗜酸性粒细胞上的高亲和力受体（0.52 nM K-d），每个细胞表达4.8 x 10(4)个位点。该受体也以较低的亲和力结合RANTES和单核细胞趋化蛋白-3，但不结合巨噬细胞炎症蛋白-1 α。Eotaxin可以使嗜酸性粒细胞对RANTES和单核细胞趋化蛋白-3的钙反应脱敏，尽管RANTES只能部分脱敏嗜酸性粒细胞对Eotaxin的钙反应。抗eotaxin单克隆抗体对人鼻息肉的免疫组化显示，某些白细胞和呼吸道上皮具有强烈的免疫反应，在eotaxin上调的部位发生嗜酸性粒细胞浸润。因此，eotaxin在人类中是一种有效的和选择性的嗜酸性粒细胞化学引诱剂，在某些炎症条件下由多种细胞类型表达。
The CC chemokine eotaxin, identified in guinea pigs and also recently in mice, may be a key element for the selective recruitment of eosinophils to certain inflamed tissues. Using a partial mouse eotaxin cDNA probe, the human eotaxin gene was cloned and found to be 61.8 and 63.2% identical at the amino acid level ro guinea pig and mouse eotaxin. Human eotaxin protein was a strong and specific eosinophil chemoattractant in vitro and was an effective eosinophil chemoattractant when injected into the skin of a rhesus monkey. Radiolabeled eotaxin was used to identify a high affinity receptor on eosinophils (0.52 nM K-d), expressed at 4.8 x 10(4) sites per cell. This receptor also bound RANTES and monocyte chemotactic protein-3 with lower affinity, but not macrophage inflammatory protein-1 alpha. Eotaxin could desensitize calcium responses of eosinophils to RANTES and monocyte chemotactic protein-3, although RANTES was able to only partially desensitize eosinophil calcium responses to eotaxin. Immunohistochemistry on human nasal polyp with antieotaxin mAbs showed that certain leukocytes as well as respiratory epithelium were intensely immunoreactive, and eosinophil infiltration occurred at sites of eotaxin upregulation. Thus eotaxin in humans is a potent and selective eosinophil chemoattractant that is expressed by a variety cell types in certain inflammatory conditions.