IL-33 is a Potent Stimulus for Eosinophil Activation

Abstract

RATIONALE: Eosinophils have an important role in asthma pathogenesis and are able to secrete exosomes which play a role in asthma pathogenesis that has not been fully defined. We hypothesized that exosomes released by eosinophils contribute to asthma pathogenesis by activating structural lung cells. METHODS: Eosinophils were purified from peripheral blood of asthmatic and healthy volunteers, and exosomes were isolated . Epithelial damage was evaluated in small airway epithelial cells in the presence of exosomes by two types of apoptosis assays, through flow cytometry and TUNEL assay by confocal microscopy. Also, wound healing assays were performed. Other functional studies such as proliferation were also carried out in bronchial smooth muscle cells. Gene and protein expression of several factors and pro-inflammatory molecules was studied in both kinds of cells after co-culture with exosomes. RESULTS: Asthmatic eosinophil-derived exosomes induced an increase in epithelial-cell apoptosis that impeded wound closure at 24 h and 48 h. In addition, muscle-cell proliferation was increased at 72 h after exosome addition and was correlated with higher phosphorylation of ERK1/2. We also found higher expression of several genes when both cell types were cultured in the presence of asthmatic exosomes: CCR3 and VEGFA in muscle cells, and CCL26, TNF, and POSTN in epithelial cells. Healthy eosinophil-derived exosomes did not exert any effect over these cell types. CONCLUSIONS: Exosomes of eosinophils from asthmatic patients participate actively in the development of the pathological features of asthma via structural lung cells. Interventions targeting exosomes could represent a new therapeutic approach in asthma.