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Specific Ag-guiding nano-vaccines attenuate neutrophil-dominant allergic asthma
Molecular Immunology ( IF 3.6 ) Pub Date : 2020-11-20 , DOI: 10.1016/j.molimm.2020.11.005
Mei-Zhen Zhao , Yan Li , Hai-Yang Han , Li-Hua Mo , Gui Yang , Zhi-Qiang Liu , Chang Ma , Ping-Chang Yang , Shuwen Liu

Polymorphonuclear neutrophils (PMN) are one fraction of the major inflammatory cells in allergic asthma (asthma, in short); the role of PMN in the asthma pathogenesis is not fully understood yet. This study aims to investigate the effects of specific Ag-guiding exosomes on suppressing the neutrophil-dominant airway inflammation. In this study, BALB/c mice were immunized with ovalbumin plus complete Freund adjuvant to induce an asthma model featured with neutrophil-dominant lung inflammation. The Ag specific PMN (sPMN)-targeting exosomes (tExo), that were exosomes carrying a complex of specific Ag/anti-CD64 Ab and Fas ligand, were constructed to be used to alleviate neutrophilic asthma in mice. We found that sPMNs were the major cellular component in bronchoalveolar lavage fluid (BALF) in asthma mice, while less than 3% PMNs in naive control mice. The sPMNs expressed higher levels of CD64, which formed complexes with Ag-specific IgG (sIgG). The sIgG/CD64 complex-carrying PMNs could be activated upon exposing to specific Ags. Exposure to tExos induced Ag-specific PMNs apoptosis. Administration of tExos efficiently suppressed experimental asthma. We conclude that a fraction of sPMN was identified in the airway of asthma mice. The sPMNs could be activated upon exposure to specific Ags. tExos could induce sPMNs apoptosis, that show the translational potential in the treatment of asthma.



中文翻译:

特定的引导银的纳米疫苗可减轻以中性粒细胞为主的过敏性哮喘

多形核中性粒细胞(PMN)是过敏性哮喘(简称哮喘)主要炎症细胞的一部分。PMN在哮喘发病机理中的作用尚不完全清楚。这项研究旨在调查特定的Ag指导外泌体在抑制中性粒细胞主导的气道炎症中的作用。在这项研究中,用卵清蛋白加弗氏完全佐剂免疫BALB / c小鼠,以诱导以中性粒细胞为主的肺部炎症为特征的哮喘模型。以携带Ag /抗CD64 Ab和Fas配体的复合体为外来体的靶向Ag特异性PMN(sPMN)的外来体(tExo)被构建用于缓解小鼠的嗜中性哮喘。我们发现sPMNs是哮喘小鼠支气管肺泡灌洗液(BALF)中的主要细胞成分,而幼稚对照小鼠中的PMN不到3%。sPMNs表达更高水平的CD64,CD64与Ag特异性IgG(sIgG)形成复合物。sIgG / CD64复合物携带的PMNs暴露于特定的Ags后可以被激活。暴露于tExos会诱导Ag特异性PMNs凋亡。施用tExos有效抑制了实验性哮喘。我们得出的结论是,在哮喘小鼠的气道中发现了一部分sPMN。sPMN可以在暴露于特定的Ag后被激活。tExos可以诱导sPMNs凋亡,显示其在哮喘治疗中的翻译潜力。我们得出的结论是,在哮喘小鼠的气道中发现了一部分sPMN。sPMN可以在暴露于特定的Ag后被激活。tExos可以诱导sPMNs凋亡,显示其在哮喘治疗中的翻译潜力。我们得出的结论是,在哮喘小鼠的气道中发现了一部分sPMN。sPMN可以在暴露于特定的Ag后被激活。tExos可以诱导sPMNs凋亡,显示其在哮喘治疗中的翻译潜力。

更新日期:2020-11-21
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