Eosinophil-derived IL-13 promotes emphysema
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 underapprecia...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Doyle, A. D., Mukherjee, M., LeSuer, W. E., Bittner, T. B., Pasha, S. M., Frere, J. J., Neely, J. L., Kloeber, J. A., Shim, K. P., Ochkur, S. I., Ho, T., Svenningsen, S., Wright, B. L., Rank, M. A., Lee, J. J., Nair, P., Jacobsen, E. A. Tags: COPD and smoking, Lung biology and experimental studies, Asthma and allergy Original Articles: Airways disease and basic science Source Type: research
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