Guangdong Provincial Key Laboratory of New Drug Screening, State Key Laboratory of Organ Failure Research, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; Department of Clinical Laboratory, Longgang E.N.T Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T., Shenzhen, China.
Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Mol Immunol. 2021 Jan;129:103-111. doi: 10.1016/j.molimm.2020.11.005. Epub 2020 Nov 20.
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.
多形核粒细胞（PMN）是过敏性哮喘（简称哮喘）中主要炎症细胞的一个亚群；PMN 在哮喘发病机制中的作用尚未完全阐明。本研究旨在探讨特异性 Ag 导向的外泌体对抑制中性粒细胞占主导地位的气道炎症的影响。在这项研究中，BALB/c 小鼠用卵清蛋白加完全弗氏佐剂免疫，诱导以中性粒细胞占主导地位的肺部炎症为特征的哮喘模型。构建了针对 Ag 特异性 PMN（sPMN）的靶向外泌体（tExo），即携带特异性 Ag/抗 CD64 Ab 和 Fas 配体复合物的外泌体，用于减轻哮喘小鼠的中性粒细胞性哮喘。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，而在正常对照小鼠中不到 3%的 PMNs。sPMNs 表达更高水平的 CD64，它与特异性 IgG（sIgG）形成复合物。暴露于特异性 Ags 后，携带 sIgG/CD64 复合物的 PMNs 可以被激活。tExos 的暴露诱导了 Ag 特异性 PMNs 的凋亡。tExos 的给药有效地抑制了实验性哮喘。我们得出结论，哮喘小鼠气道中鉴定出了一部分 sPMN。sPMNs 可以在暴露于特异性 Ags 后被激活。tExos 可以诱导 sPMNs 凋亡，这显示了在哮喘治疗中的转化潜力。
