Hepatocyte Growth Factor Suppresses Production of Reactive Oxygen Species and Release of Eosinophil-Derived Neurotoxin from Human Eosinophils
Hepatocyte Growth Factor Suppresses Production of Reactive Oxygen Species and Release of Eosinophil-Derived Neurotoxin from Human Eosinophils
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DOI：
10.1159/000144041
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发表时间：
2008-01-01
影响因子：
2.8
通讯作者：
Chihara, Junichi
中科院分区：
文献类型：
--
作者：
Ito, Wataru;Takeda, Masahide;Chihara, Junichi
背景资料：活性氧（ROS）和嗜酸性粒细胞颗粒蛋白（如嗜酸性粒细胞衍生的神经毒素（EDN））是已知的支气管组织损伤和导致气道高反应性（AHR）在哮喘。肝细胞生长因子（HGF）是一种多功能因子，具有多种生物学活性.在我们以前的研究中，我们发现HGF抑制哮喘小鼠模型的过敏性气道炎症和AHR。然而，关于HGF在哮喘中的抗过敏作用的详细机制的报道很少。在这项研究中，我们研究了重组肝细胞生长因子调节人嗜酸性粒细胞产生活性氧和释放EDN的潜力。方法：采用改良的CD 16阴性选择法从轻度嗜酸性粒细胞增多症患者中分离嗜酸性粒细胞。我们用流式细胞术研究了嗜酸性粒细胞活化标志物CD 69在嗜酸性粒细胞上的表达。此外，使用鲁米诺依赖性化学发光分析来自嗜酸性粒细胞的ROS产生，并通过ELISA测量EDN释放。结果：HGF抑制IL-5诱导的人嗜酸性粒细胞CD 69表达、ROS产生和EDN释放的上调。结论：总之，这些数据表明，在哮喘中，HGF至少通过抑制ROS产生和嗜酸性粒细胞释放EDN来减轻过敏性气道炎症和AHR。版权所有（C）2008 S. Karger AG，巴塞尔
Background: Reactive oxygen species (ROS) and eosinophilic granule proteins such as eosinophil-derived neurotoxin (EDN) are known to damage bronchial tissue and cause airway hyperresponsiveness (AHR) in asthma. Hepatocyte growth factor (HGF) regulates various biological activities and is known to be a multifunctional factor. In our previous study, we found that HGF suppressed allergic airway inflammation and AHR in a murine model of asthma. However, there have been few reports regarding the detailed mechanism of the anti-allergic effect of HGF in asthma. In this study, we investigated the potential of recombinant HGF to regulate the production of ROS and the release of EDN from human eosinophils. Methods: Eosinophils were isolated from subjects with mild eosinophilia by modified CD16-negative selection. We investigated the expression of CD69, an activation marker of eosinophils, on eosinophils, using flow cytometry. Further, ROS production from eosinophils was analyzed using luminol-dependent chemiluminescence, and EDN release was measured by ELISA. Results: Treatment with HGF suppressed interleukin-5-induced upregulation of CD69 expression, ROS production and EDN release from human eosinophils. Conclusion: Taken together, these data suggest that in asthma, HGF attenuates allergic airway inflammation and AHR through at least the suppression of ROS production and EDN release from eosinophils. Copyright (C) 2008 S. Karger AG, Basel