Exosomes from eosinophils autoregulate and promote eosinophil functions
Exosomes from eosinophils autoregulate and promote eosinophil functions
复制标题
DOI：
10.1189/jlb.3ab0516-233rr
复制
发表时间：
2017-05-01
影响因子：
5.5
通讯作者：
del Pozo, Victoria
中科院分区：
文献类型：
--
作者：
Antonio Canas, Jose;Sastre, Beatriz;del Pozo, Victoria
嗜酸性粒细胞能够分泌在哮喘发病机制中具有不确定作用的外泌体。我们假设嗜酸性粒细胞释放的外泌体能够自动调节和促进嗜酸性粒细胞的功能。从外周血中纯化哮喘患者（n = 58）和健康志愿者（n = 16）的嗜酸性粒细胞，并从哮喘和健康人群的嗜酸性粒细胞中分离和定量外泌体。在存在或不存在来自健康和哮喘个体的外来体的情况下，用嗜酸性粒细胞进行细胞凋亡、粘附、粘附分子表达和迁移测定。活性氧（ROS）通过流式细胞术与细胞内的荧光探针和一氧化氮（NO）和比色试剂盒进行评估。此外，外泌体蛋白通过质谱分析。嗜酸性粒细胞来源的外泌体诱导嗜酸性粒细胞上NO和ROS产生增加。此外，外泌体可以作为嗜酸性粒细胞的趋化因子，它们产生细胞粘附的增加，引起粘附分子如ICAM-1和整合素α 2的特异性增加。来自健康和哮喘个体的外泌体之间的蛋白质含量在两组中似乎相似。总之，我们发现来自哮喘患者嗜酸性粒细胞的外泌体可以改变与哮喘发病机制相关的几种特定嗜酸性粒细胞功能，并且它们可以从根本上促进哮喘的发展和维持。
Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma (n = 58) and healthy volunteers (n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin alpha 2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma.