Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia.
Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia.
复制标题
趋化因子嗜酸性粒细胞趋化因子的靶向破坏可部分减少抗原诱导的组织嗜酸性粒细胞增多。
DOI：
10.1084/jem.185.4.785
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发表时间：
1997-02-17
影响因子：
15.3
通讯作者：
Leder, P
中科院分区：
文献类型：
--
作者：
Rothenberg, M E;MacLean, J A;Pearlman, E;Luster, A D;Leder, P
趋化因子是一大类调节白细胞运输的趋化细胞因子，最近被证明可以抑制人类免疫缺陷病毒进入细胞。Eotaxin是一种C-C趋化因子，与各种炎症性疾病中嗜酸性粒细胞的募集有关，与所有其他嗜酸性粒细胞趋化剂不同，它是嗜酸性粒细胞特异性的。然而，鉴于大量的化学引诱剂对嗜酸性粒细胞有活性，eotaxin在体内是否有重要作用尚不清楚。此外，尚不清楚为什么在没有嗜酸性粒细胞炎症的健康状态下存在eotaxin的组成性表达。为了开始确定eotaxin在基线和嗜酸性粒细胞介导的疾病过程中的重要性，我们使用靶向基因破坏来产生eotaxin缺乏的小鼠。这些小鼠表明，eotaxin增强了哮喘和间质角膜炎模型抗原激发后早期（但不是晚期）嗜酸性粒细胞募集的强度。令人惊讶的是，eotaxin在调节外周循环中嗜酸性粒细胞组成数量方面的作用也得到了证实。这些结果表明，eotaxin在外周血和抗原诱导的组织嗜酸性粒细胞增多症的产生中起着重要作用。
The chemokines are a large group of chemotactic cytokines that regulate leukocyte trafficking and have recently been shown to inhibit human immunodeficiency virus entry into cells. Eotaxin is a C–C chemokine implicated in the recruitment of eosinophils in a variety of inflammatory disorders and, unlike all other eosinophil chemoattractants, is eosinophil specific. However, given the large number of chemoattractants that have activities on eosinophils, it is unclear whether eotaxin has an important role in vivo. Furthermore, it remains unclear why there is constitutive expression of eotaxin in healthy states in the absence of eosinophilic inflammation. To begin to determine the significance of eotaxin at baseline and during eosinophil-mediated disease processes, we have used targeted gene disruption to generate mice that are deficient in eotaxin. Such mice demonstrate that eotaxin enhances the magnitude of the early (but not late) eosinophil recruitment after antigen challenge in models of asthma and stromal keratitis. Surprisingly, a role for eotaxin in regulating the constitutive number of eosinophils in the peripheral circulation is also demonstrated. These results indicate a contributory role for eotaxin in the generation of peripheral blood and antigen-induced tissue eosinophilia.