Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Allergy Center, Saitama Medical University, Saitama, Japan.
Front Immunol. 2018 Sep 28;9:2220. doi: 10.3389/fimmu.2018.02220. eCollection 2018.
Eosinophils are involved in the development of asthma exacerbation. Recent studies have suggested that sputum and blood eosinophil counts are important factors for predicting asthma exacerbation. In severe eosinophilic asthma, anti-interleukin (IL)-5 monoclonal antibody decreases blood eosinophil count and asthma exacerbation frequency. However, even in the absence of IL-5, eosinophilic airway inflammation can be sufficiently maintained by the T helper (Th) 2 network, which comprises a cascade of vascular cell adhesion molecule-1/CC chemokines/eosinophil growth factors, including granulocyte-macrophage colony-stimulating factor (GM-CSF). Periostin, an extracellular matrix protein and a biomarker of the Th2 immune response in asthma, directly activates eosinophils . A major cause of asthma exacerbation is viral infection, especially rhinovirus (RV) infection. The expression of intercellular adhesion molecule (ICAM)-1, a cellular receptor for the majority of RVs, on epithelial cells is increased after RV infection, and adhesion of eosinophils to ICAM-1 can upregulate the functions of eosinophils. The expressions of cysteinyl leukotrienes (cysLTs) and CXCL10 are upregulated in virus-induced asthma. CysLTs can directly provoke eosinophilic infiltration and activate eosinophils . Furthermore, eosinophils express the CXC chemokine receptor 3, and CXCL10 activates eosinophils . Both eosinophils and neutrophils contribute to the development of severe asthma or asthma exacerbation. IL-8, which is an important chemoattractant for neutrophils, is upregulated in some cases of severe asthma. Lipopolysaccharide (LPS), which induces IL-8 from epithelial cells, is also increased in the lower airways of corticosteroid-resistant asthma. IL-8 or LPS-stimulated neutrophils increase the transbasement membrane migration of eosinophils, even in the absence of chemoattractants for eosinophils. Therefore, eosinophils are likely to contribute to the development of asthma exacerbation through several mechanisms, including activation by Th2 cytokines, such as IL-5 or GM-CSF or by virus infection-related proteins, such as CXCL10, and interaction with other cells, such as neutrophils.
嗜酸性粒细胞参与哮喘恶化的发展。最近的研究表明，痰和血液嗜酸性粒细胞计数是预测哮喘恶化的重要因素。在严重嗜酸性粒细胞性哮喘中，抗白细胞介素（IL）-5 单克隆抗体可降低血液嗜酸性粒细胞计数和哮喘恶化频率。然而，即使没有 IL-5，嗜酸性粒细胞气道炎症也可以通过 Th2 网络（包括血管细胞黏附分子-1/CC 趋化因子/嗜酸性粒细胞生长因子级联反应，包括粒细胞-巨噬细胞集落刺激因子（GM-CSF））得到充分维持。periostin 是哮喘中 Th2 免疫反应的细胞外基质蛋白和生物标志物，可直接激活嗜酸性粒细胞。哮喘恶化的一个主要原因是病毒感染，尤其是鼻病毒（RV）感染。上皮细胞中细胞间黏附分子（ICAM）-1 的表达在 RV 感染后增加，而嗜酸性粒细胞与 ICAM-1 的黏附可上调嗜酸性粒细胞的功能。病毒诱导的哮喘中胱抑素白三烯（cysLTs）和 CXCL10 的表达上调。cysLTs 可直接引发嗜酸性粒细胞浸润并激活嗜酸性粒细胞。此外，嗜酸性粒细胞表达 CXC 趋化因子受体 3，而 CXCL10 可激活嗜酸性粒细胞。嗜酸性粒细胞和中性粒细胞都有助于严重哮喘或哮喘恶化的发展。白细胞介素（IL）-8 是中性粒细胞的重要趋化因子，在某些严重哮喘病例中上调。上皮细胞诱导的 IL-8 的脂多糖（LPS）在皮质类固醇耐药性哮喘的下气道中也增加。IL-8 或 LPS 刺激的中性粒细胞增加嗜酸性粒细胞的跨基底膜迁移，即使没有嗜酸性粒细胞的趋化因子也是如此。因此，嗜酸性粒细胞可能通过几种机制有助于哮喘恶化的发展，包括 Th2 细胞因子（如 IL-5 或 GM-CSF）或与病毒感染相关的蛋白（如 CXCL10）的激活，以及与其他细胞（如中性粒细胞）的相互作用。
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