Eosinophil-derived IL-13 promotes emphysema Academic Article uri icon

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abstract

  • The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.Airspace enlargement was identified in I5/hE2 mice and was dependent on eosinophils. Examination of I5/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed, in vitro, that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 production. Airspace enlargement in I5/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1 s.A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.

authors

  • Doyle, Alfred D
  • Mukherjee, Manali
  • LeSuer, William E
  • Bittner, Tyler B
  • Pasha, Saif M
  • Frere, Justin J
  • Neely, Joseph L
  • Kloeber, Jake A
  • Shim, Kelly P
  • Ochkur, Sergei I
  • Ho, Terence
  • Svenningsen, Sarah
  • Wright, Benjamin L
  • Rank, Matthew A
  • Lee, James J
  • Nair, Parameswaran Krishna
  • Jacobsen, Elizabeth A

publication date

  • May 2019