Selected article for: "cell death and lung epithelial cell line"
Author: Pandolfi, Laura; Bozzini, Sara; Frangipane, Vanessa; Percivalle, Elena; De Luigi, Ada; Violatto, Martina Bruna; Lopez, Gianluca; Gabanti, Elisa; Carsana, Luca; D’Amato, Maura; Morosini, Monica; De Amici, Mara; Nebuloni, Manuela; Fossali, Tommaso; Colombo, Riccardo; Saracino, Laura; Codullo, Veronica; Gnecchi, Massimiliano; Bigini, Paolo; Baldanti, Fausto; Lilleri, Daniele; Meloni, Federica
Title: Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in post-COVID-19 fibrosis
  • Cord-id: 1xzkfl8g
  • Document date: 2020_11_9
    • ID: 1xzkfl8g
    Snippet: The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Neutrophils activated with PMA (PMA-Neu), a stimulus known to induce NETs format
    Document: The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Neutrophils activated with PMA (PMA-Neu), a stimulus known to induce NETs formation, induce both EMT and cell death in the lung epithelial cell line, A549. Notably, NETs isolated from PMA-Neu induce EMT without cell damage. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs. Thus, we tested in an in vitro alveolar model the hypothesis that virus-induced NET may drive EMT. Co-culturing A549 at air-liquid interface with alveolar macrophages, neutrophils and SARS-CoV2, we demonstrated a significant induction of the EMT in A549 together with high concentration of NETs, IL8 and IL1β, best-known inducers of NETosis. Lung tissues of COVID-19 deceased patients showed that epithelial cells are characterized by increased mesenchymal markers. These results show for the first time that NETosis plays a major role in triggering lung fibrosis in COVID-19 patients.

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