Find Paper, Faster
Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Low Dose Hyperoxia Primes Airways for Fibrosis in Mice after Influenza A Infection
American Journal of Physiology-Lung Cellular and Molecular Physiology  (IF5.464),  Pub Date : 2021-07-29, DOI: 10.1152/ajplung.00289.2020
Andrew M Dylag, Jeannie Haak, Rachel Warren, Min Yee, Gloria S Pryhuber, Michael A. O'Reilly

It is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection. We recently reported a new, low-dose hyperoxia mouse model (40% for 8 days; 40x8) that causes a transient change in lung function that resolves, rendering 40x8 adult animals functionally indistinguishable from room air controls. Here we reported that when infected with IAV, 40x8 mice display an early transient activation of TGFβ signaling and later airway hyperreactivity associated with peribronchial inflammation (profibrotic macrophages) and fibrosis compared to infected room air controls, suggesting neonatal oxygen induced hidden molecular changes that prime the lung for hyperreactive airways disease. While searching for potential activators of TGFβ signaling, we discovered that thrombospondin-1 (TSP-1) is elevated in naïve 40x8 mice compared to controls and localized to lung megakaryocytes and platelets before and during IAV infection. Elevated TSP-1 was also identified in human autopsy samples of former preterm infants with bronchopulmonary dysplasia. These findings reveal how low doses of oxygen that do not durably change lung function may prime it for hyperreactive airways disease by changing expression of genes, such as TSP-1, thus helping to explain why former preterm infants who have normal lung function are susceptible to airway obstruction and increased morbidity after viral infection.