IL-13 induces eosinophil recruitment into the lung by an IL-5-and eotaxin-dependent mechanism
IL-13 induces eosinophil recruitment into the lung by an IL-5-and eotaxin-dependent mechanism
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DOI：
10.1067/mai.2001.118600
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发表时间：
2001-10-01
影响因子：
14.2
通讯作者：
Rothenberg, ME
中科院分区：
文献类型：
--
作者：
Pope, SM;Brandt, EB;Rothenberg, ME
背景：IL-13诱导哮喘的几个特征，包括气道嗜酸性粒细胞增多、气道高反应性和粘液分泌过多；然而，所涉及的机制在很大程度上是未知的。目的：我们假设il- 13诱导的肺部炎症变化部分依赖于IL-5和eotaxin这两种嗜酸性粒细胞选择性细胞因子。方法：重组小鼠IL-13经鼻内给药，反复给药至哮喘特征出现。为了分析IL-5和eotaxin的作用，我们将Balb/C背景的eotaxin基因靶向、IL-5基因靶向、eotaxin/IL-5双缺陷、IL-5转基因和野生型小鼠置于实验环境中。结果：发现IL-13介导的气道嗜酸性粒细胞的诱导独立于血液或骨髓嗜酸性粒细胞的发生，表明IL-13诱导的气道炎症主要是由IL-13在肺部的局部作用介导的。与野生型对照相比，il -5缺陷小鼠肺组织和支气管肺泡灌洗液中的嗜酸性粒细胞募集明显减少。因此，与野生型小鼠相比，IL-13传递给IL-5转基因小鼠导致气道嗜酸性粒细胞大量增加。有趣的是，在eotaxin缺陷小鼠的支气管肺泡灌洗液中，il -13诱导的嗜酸性粒细胞未受损；然而，这些小鼠对IL-13的反应并没有产生显著的组织嗜酸性粒细胞增多。最后，il -13诱导的粘液分泌不受IL-5或eotaxin存在的影响，这表明il -13诱导的粘液分泌与气道嗜酸性粒细胞分离的机制。结论：il -13诱导哮喘表型的选择性组分-气道嗜酸性粒细胞增多而非粘液分泌-受IL-5和eotaxin的差异调节。IL-13在整个肺中诱导嗜酸性粒细胞需要IL-5，而eotaxin调节气道嗜酸性粒细胞的分布。
Background: IL-13 induces several characteristic features of asthma, including airway eosinophilia, airway hyperresponsiveness, and mucus overproduction; however, the mechanisms involved are largely unknown.Objective: We hypothesized that IL-13-induced inflammatory changes in the lung were dependent in part on IL-5 and eotaxin, two eosinophil-selective cytokines.Methods: Recombinant murine IL-13 was repeatedly administered to the lung by intranasal delivery until the characteristic features of asthma developed. To analyze the role of IL-5 and eotaxin, we subjected eotaxin gene-targeted, IL-5 gene-targeted, eotaxin/IL-5-double-deficient, IL-5 transgenic, and wild-type mice, of the Balb/C background to the experimental regime.Results: The induction of IL-13-mediated airway eosinophilia was found to occur independently of eosinophilia in the blood or bone marrow, indicating that IL-13-induced airway inflammation is primarily mediated by local effects of IL-13 in the lung. Eosinophil recruitment into both the lung tissue and bronchoalveolar lavage fluid was markedly attenuated in IL-5-deficient mice in comparison with wild-type controls. Accordingly, IL-13 delivery to IL-5 transgenic mice resulted in a large increase in airway eosinophils in comparison with wild-type mice. Interestingly, IL-13-induced eosinophilia in the bronchoalveolar lavage fluid of eotaxin-deficient mice was not impaired; however, these same mice failed to mount a significant tissue eosinophilia in response to IL-13. Finally, IL-13-induced mucus production was not affected by the presence of IL-5 or eotaxin, suggesting that IL-13-induced mucus secretion is mechanistically dissociated from airway eosinophilia.Conclusion: Selective components of the IL-13-induced asthma phenotype-airway eosinophilia but not mucus secretion-are differentially regulated by IL-5 and eotaxin. IL-5 is required for IL-13 to induce eosinophilia throughout the lung, whereas eotaxin regulates the distribution of airway eosinophils.