Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia
Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia
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DOI：
10.1038/nm0496-449
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发表时间：
1996-04-01
期刊：
影响因子：
82.9
通讯作者：
Luster, AD
中科院分区：
文献类型：
--
作者：
GarciaZepeda, EA;Rothenberg, ME;Luster, AD
嗜酸性粒细胞趋化因子是一种嗜酸性粒细胞特异性趋化因子，最近在哮喘的啮齿动物模型和宿主对肿瘤的反应中被发现。为了确定类似的分子是否可能在以嗜酸性粒细胞增多症为特征的人类炎症性疾病中发挥作用，我们分离了人类嗜酸性粒细胞趋化蛋白基因。我们证明人类嗜酸性粒细胞趋化因子是细胞因子刺激的上皮细胞和内皮细胞的早期反应基因，并由白细胞介素3诱导外周血嗜酸性粒细胞。嗜酸性粒细胞趋化因子对嗜酸性粒细胞有直接趋化作用，但对单核细胞和中性粒细胞无直接趋化作用。嗜酸性粒细胞趋化因子信使RNA在炎症性肠病(溃疡性结肠炎和克罗恩病)患者的皮损中显著积聚，而在憩室炎患者的皮损中则不明显。这些结果现在提供了一种涉及嗜酸性粒细胞的机制来解释在各种人类疾病中看到的嗜酸性粒细胞渗透；因此，嗜酸性粒细胞趋化因子拮抗剂可能是一种治疗某些以组织嗜酸性粒细胞增多症为特征的人类疾病的新方法。
Eotaxin is an eosinophil-specific chemoattractant that has been recently identified in rodent models of asthma and host response against tumors. To determine whether a similar molecule might play a role in human inflammatory diseases characterized by eosinophilia, we isolated the human eotaxin gene. We demonstrate that human eotaxin is an early response gene of cytokine-stimulated epithelial and endothelial cells, and is induced in peripheral blood eosinophils by interleukin-3. Eotaxin is directly chemotactic for eosinophils, but not mononuclear cells or neutrophils. Eotaxin messenger RNA accumulates markedly in the lesions of patients with inflammatory bowel disease (ulcerative colitis and Crohn's disease), but not in the lesions of patients with diverticulitis. These results now provide a mechanism involving eotaxin to explain the eosinophil infiltration seen in a variety of human diseases; as such, an eotaxin antagonist may be a novel therapy for certain human diseases characterized by tissue eosinophilia.