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Galectin-9 attenuates elastase-induced emphysema by reducing neutrophil chemotaxis in mice

Yuko Horio, Keisuke Kojima, Naoki Saita, Yohei Migiyama, Aiko Masunaga, Hidenori Ichiyasu, Kazuhiko Fujii, Hirotsugu Kohrogi
European Respiratory Journal 2016 48: PA4013; DOI: 10.1183/13993003.congress-2016.PA4013
Yuko Horio
1Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan
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Keisuke Kojima
1Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan
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Naoki Saita
1Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan
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Yohei Migiyama
1Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan
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Aiko Masunaga
1Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan
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Hidenori Ichiyasu
1Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan
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Kazuhiko Fujii
1Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan
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Hirotsugu Kohrogi
1Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan
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Abstract

Background: Pulmonary emphysema is characterized by irreversible airflow obstruction, inflammation, oxidative stress imbalance and lung remodeling, resulting in reduced lung function and a lower quality of life. Galectin (Gal)-9 plays a crucial role in the modulation of innate and adaptive immunity.

Objectives: To investigate whether Gal-9 reduce pulmonary inflammation and lung remodeling in experimental emphysema mouse model.

Methods: Emphysema was induced in C57BL/6 mice by intratracheal administration of porcine pancreatic elastase (PPE) (2 IU) once on day 0. Gal-9 (3 µg/body) or PBS was administered subcutaneously, once daily from day -1 to day 5.

Results: Gal-9 suppressed pathological changes of emphysema induced by PPE. The mean linear intercept length (Lm) of Gal-9-treated emphysema mice was lower than that of PBS-treated emphysema mice (66.1 ± 3.3 µm vs. 118.8 ± 14.8 µm, respectively, P < 0.01). Gal-9 decreased neutrophils and matrix metalloproteinase (MMP)-9 in the bronchoalveolar lavage fluid of emphysema mice, but did not reduce levels of pro-inflammatory cytokines and neutrophil chemokines, keratinocyte-derived cytokine (KC), chemokine ligand-2 and chemokine ligand-5. Interestingly, functional assays revealed that Gal-9 inhibited chemotaxis of PMN towards KC. In Gal-9 knockout mice, Lm after PPE administration was significantly increased compared with that in wild type mice.

Conclusion: Subcutaneous administration of Gal-9 decreases the severity of elastase-induced inflammation and airspace enlargement by inhibiting the chemotaxis of neutrophils and decreasing MMP-9. These results indicate that Gal-9 may be an effective therapeutic agent for the treatment of emphysema and COPD.

  • Animal models
  • COPD - management
  • Inflammation
  • Copyright ©the authors 2016
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Galectin-9 attenuates elastase-induced emphysema by reducing neutrophil chemotaxis in mice
Yuko Horio, Keisuke Kojima, Naoki Saita, Yohei Migiyama, Aiko Masunaga, Hidenori Ichiyasu, Kazuhiko Fujii, Hirotsugu Kohrogi
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4013; DOI: 10.1183/13993003.congress-2016.PA4013

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Galectin-9 attenuates elastase-induced emphysema by reducing neutrophil chemotaxis in mice
Yuko Horio, Keisuke Kojima, Naoki Saita, Yohei Migiyama, Aiko Masunaga, Hidenori Ichiyasu, Kazuhiko Fujii, Hirotsugu Kohrogi
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4013; DOI: 10.1183/13993003.congress-2016.PA4013
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