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

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.