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Eosinophil-derived IL-13 promotes emphysema.

Alfred D Doyle1, Manali Mukherjee2, William E LeSuer3

  • 1Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, AZ, USA.

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|February 8, 2019
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Summary
This summary is machine-generated.

Eosinophils drive emphysema by promoting matrix metalloprotease-12 (MMP-12) production. This study reveals eosinophil-driven inflammation as a key factor in chronic obstructive pulmonary disease (COPD) and asthma pathogenesis.

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Area of Science:

  • Pulmonary immunology
  • Inflammatory lung diseases

Background:

  • Chronic airway diseases like COPD involve complex inflammatory responses.
  • The precise mechanisms linking inflammation to emphysema, particularly the role of eosinophils, are not fully understood.

Purpose of the Study:

  • To investigate the hypothesis that lung eosinophilia contributes to airspace enlargement in a mouse model and emphysema in COPD patients.
  • To elucidate eosinophil-dependent mechanisms in the development of emphysema.

Main Methods:

  • Utilized a transgenic mouse model (I5/hE2) of chronic type 2 pulmonary inflammation.
  • Collected human sputum samples for translational studies.
  • Assessed airspace enlargement, eosinophil counts, matrix metalloprotease (MMP)-12 levels, and interleukin (IL)-4/13 in mice and patients.
  • Performed in vitro experiments to determine the role of eosinophil-derived cytokines on macrophage MMP-12 production.

Main Results:

  • Eosinophils were essential for airspace enlargement in the I5/hE2 mouse model.
  • Elevated MMP-12 levels were found in bronchoalveolar lavage fluid of I5/hE2 mice.
  • Eosinophil-derived IL-13 stimulated MMP-12 production by alveolar macrophages in vitro.
  • Airspace enlargement in mice depended on MMP-12 and eosinophil-derived IL-4/13.
  • Human patients with sputum eosinophilia and emphysema showed elevated MMP-12 levels, negatively correlating with lung function (forced expiratory volume in 1 second).

Conclusions:

  • Chronic type 2 pulmonary inflammation, driven by eosinophils and MMP-12, causes airspace enlargement in a mouse model.
  • Lung eosinophilia is associated with elevated MMP-12 in COPD patients and predicts emphysema.
  • Eosinophils represent an underappreciated mechanism contributing to pathologies in asthma and COPD.