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.
| Original language | English (US) |
|---|---|
| Journal | The European respiratory journal |
| Volume | 53 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2019 |
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ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
Eosinophil-derived IL-13 promotes emphysema. / 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; Rank, Matthew A; Lee, James J.; Nair, Parameswaran; Jacobsen, Elizabeth A.
In: The European respiratory journal, Vol. 53, No. 5, 01.05.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Eosinophil-derived IL-13 promotes emphysema
AU - Doyle, Alfred D.
AU - Mukherjee, Manali
AU - LeSuer, William E.
AU - Bittner, Tyler B.
AU - Pasha, Saif M.
AU - Frere, Justin J.
AU - Neely, Joseph L.
AU - Kloeber, Jake A.
AU - Shim, Kelly P.
AU - Ochkur, Sergei I.
AU - Ho, Terence
AU - Svenningsen, Sarah
AU - Wright, Benjamin
AU - Rank, Matthew A
AU - Lee, James J.
AU - Nair, Parameswaran
AU - Jacobsen, Elizabeth A.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85067293565&partnerID=8YFLogxK
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U2 - 10.1183/13993003.01291-2018
DO - 10.1183/13993003.01291-2018
M3 - Article
VL - 53
JO - European Respiratory Journal
JF - European Respiratory Journal
SN - 0903-1936
IS - 5
ER -