Autophagy induces eosinophil extracellular traps formation and allergic airway inflammation in a murine asthma model. Issue 1 (17th June 2019)

• Record Type: Journal Article
• Authors: Silveira, Josiane Silva; Antunes, Géssica Luana; Kaiber, Daniela Benvenutti; da Costa, Mariana Severo; Ferreira, Fernanda Silva; Marques, Eduardo Peil; Schmitz, Felipe; Gassen, Rodrigo Benedetti; Breda, Ricardo Vaz; Wyse, Angela T. S.; Stein, Renato Tetelbom; Pitrez, Paulo Márcio; da Cunha, Aline Andrea
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 1(2020:Jan.)
• Page Start: 267
• Page End: 280
• Publication Date: 2019-06-17
• Subjects: asthma -- autophagy -- eosinophil extracellular traps -- eosinophils -- inflammation; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28966
• Languages: English
• ISSNs: 0021-9541

Abstract

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. Abstract : We demonstrated that treatment with autophagy inhibitor 3‐methyladenine (3‐MA) reduced eosinophil extracellular traps formation in bronchoalveolar lavage fluid (BALF). This is the first study to demonstrate that viable eosinophils release mitochondrial DNA dependent of autophagy in the airway of a murine model of asthma.