The effect of hepatocyte growth factor on secretory functions in human eosinophils
The effect of hepatocyte growth factor on secretory functions in human eosinophils
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肝细胞生长因子对人嗜酸性粒细胞分泌功能的影响
DOI：
10.1016/j.cyto.2016.08.013
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发表时间：
2016
期刊：
影响因子：
3.8
通讯作者：
Hirokawa M
中科院分区：
文献类型：
--
作者：
Yamauchi Y;Ueki S;Konno Y;Ito W;Takeda M;Nakamura Y;Nishikawa J;Moritoki Y;Omokawa A;Saga T;Hirokawa M
肝细胞生长因子（HGF）最初被鉴定为成熟肝细胞的有效有丝分裂原，现在被认为是炎症和免疫反应的体液介质。以往的研究表明，HGF负性调节过敏性气道炎症。鉴于嗜酸性粒细胞在哮喘发病机制中的作用，特别是在气道重塑中作为促纤维化介质的丰富来源，本研究探讨了HGF对不同类型嗜酸性粒细胞分泌功能的影响。我们发现HGF显著抑制IL-5诱导的人嗜酸性粒细胞分泌TGF-β和VEGF。抑制作用与TGF-β转录无关;相反，它与超微结构颗粒排空和细胞内TGF-β含量损失有关，表明HGF抑制了碎片脱颗粒过程。还研究了HGF对介导细胞溶解性脱粒的细胞外陷阱细胞死亡（ETosis）的影响;然而，固定化IgG或佛波醇肉豆蔻酸酯乙酸酯诱导的ETosis仅被HGF最小程度地减弱。这些结果揭示了HGF对嗜酸性粒细胞分泌功能的不同途径的影响，也为HGF在过敏性炎症发病机制中的作用提供了新的见解。
Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-β and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-β transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF-β contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation.