自噬诱导小鼠哮喘模型中嗜酸性粒细胞细胞外陷阱形成和过敏性气道炎症
2021/02/09
摘要
研究表明自噬参与炎症性疾病的免疫病理学，然而，自噬在哮喘和嗜酸性粒细胞细胞外诱捕网（EETs）释放中的作用知之甚少。我们试图在一个实验性哮喘模型中研究自噬参与EETs释放和肺部炎症。用卵清蛋白致敏小鼠，随后进行OVA刺激。在用OVA刺激之前，用自噬抑制剂3-甲基腺嘌呤（3-MA）处理小鼠。我们发现3-MA治疗降低了肺内嗜酸性粒细胞数量、嗜酸性粒细胞过氧化物酶（EPO）活性、杯状细胞增生、促炎细胞因子和核因子ΚΒP65免疫含量。此外，3-MA能够改善氧化应激、线粒体能量代谢和Na+ , K+ -ATP酶活性。我们证明了自噬抑制剂3-MA的治疗减少了气道中EETs的形成。根据我们的结果，3-MA治疗可能是减少哮喘中肺部炎症、氧化应激、线粒体损伤和EETs形成的替代方案。
Autophagy induces eosinophil extracellular traps formation and allergic airway inflammation in a murine asthma model
Josiane Silva Silveira, Géssica Luana Antunes, Daniela Benvenutti Kaiber, Mariana Severo da Costa, Fernanda Silva Ferreira, Eduardo Peil Marques, Felipe Schmitz, Rodrigo Benedetti Gassen, Ricardo Vaz Breda, Angela T S Wyse, Renato Tetelbom Stein, Paulo Márcio Pitrez, Aline Andrea da Cunha
Abstract
Studies have shown autophagy participation in the immunopathology of inflammatory diseases. However, autophagy role in asthma and in eosinophil extracellular traps (EETs) release is poorly understood. Here, we attempted to investigate the autophagy involvement in EETs release and in lung inflammation in an experimental asthma model. Mice were sensitized with ovalbumin (OVA), followed by OVA challenge. Before the challenge with OVA, mice were treated with an autophagy inhibitor, 3-methyladenine (3-MA). We showed that 3-MA treatment decreases the number of eosinophils, eosinophil peroxidase (EPO) activity, goblet cells hyperplasia, proinflammatory cytokines, and nuclear factor kappa B (NFκB) p65 immunocontent in the lung. Moreover, 3-MA was able to improve oxidative stress, mitochondrial energy metabolism, and Na+ , K+ -ATPase activity. We demonstrated that treatment with autophagy inhibitor 3-MA reduced EETs formation in the airway. On the basis of our results, 3-MA treatment can be an interesting alternative for reducing lung inflammation, oxidative stress, mitochondrial damage, and EETs formation in asthma.
研究表明自噬参与炎症性疾病的免疫病理学，然而，自噬在哮喘和嗜酸性粒细胞细胞外诱捕网（EETs）释放中的作用知之甚少。我们试图在一个实验性哮喘模型中研究自噬参与EETs释放和肺部炎症。用卵清蛋白致敏小鼠，随后进行OVA刺激。在用OVA刺激之前，用自噬抑制剂3-甲基腺嘌呤（3-MA）处理小鼠。我们发现3-MA治疗降低了肺内嗜酸性粒细胞数量、嗜酸性粒细胞过氧化物酶（EPO）活性、杯状细胞增生、促炎细胞因子和核因子ΚΒP65免疫含量。此外，3-MA能够改善氧化应激、线粒体能量代谢和Na+ , K+ -ATP酶活性。我们证明了自噬抑制剂3-MA的治疗减少了气道中EETs的形成。根据我们的结果，3-MA治疗可能是减少哮喘中肺部炎症、氧化应激、线粒体损伤和EETs形成的替代方案。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(J Cell Physiol . 2020 Jan;235(1):267-280.doi: 10.1002/jcp.28966)
(J Cell Physiol . 2020 Jan;235(1):267-280.doi: 10.1002/jcp.28966)
Autophagy induces eosinophil extracellular traps formation and allergic airway inflammation in a murine asthma model
Josiane Silva Silveira, Géssica Luana Antunes, Daniela Benvenutti Kaiber, Mariana Severo da Costa, Fernanda Silva Ferreira, Eduardo Peil Marques, Felipe Schmitz, Rodrigo Benedetti Gassen, Ricardo Vaz Breda, Angela T S Wyse, Renato Tetelbom Stein, Paulo Márcio Pitrez, Aline Andrea da Cunha
Abstract
Studies have shown autophagy participation in the immunopathology of inflammatory diseases. However, autophagy role in asthma and in eosinophil extracellular traps (EETs) release is poorly understood. Here, we attempted to investigate the autophagy involvement in EETs release and in lung inflammation in an experimental asthma model. Mice were sensitized with ovalbumin (OVA), followed by OVA challenge. Before the challenge with OVA, mice were treated with an autophagy inhibitor, 3-methyladenine (3-MA). We showed that 3-MA treatment decreases the number of eosinophils, eosinophil peroxidase (EPO) activity, goblet cells hyperplasia, proinflammatory cytokines, and nuclear factor kappa B (NFκB) p65 immunocontent in the lung. Moreover, 3-MA was able to improve oxidative stress, mitochondrial energy metabolism, and Na+ , K+ -ATPase activity. We demonstrated that treatment with autophagy inhibitor 3-MA reduced EETs formation in the airway. On the basis of our results, 3-MA treatment can be an interesting alternative for reducing lung inflammation, oxidative stress, mitochondrial damage, and EETs formation in asthma.
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痰肥大细胞/嗜碱性粒细胞基因表达与重症哮喘的炎症和临床特征相关
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哮喘患者嗜酸性粒细胞增多症对严重COVID-19疾病有保护作用
