Galectin‐3 mediates chronic airway allergic inflammation and airway remodeling

Abstract

The role played by Galectin‐3 (Gal‐3) in airway remodeling, a feature of chronic asthma that leads to airway dysfunction and poor clinical outcome in humans, was investigated in a murine model of asthma. Wild‐type (WT) and Gal‐3 knock‐out (KO) mice were subjected to repetitive allergen challenge with ovalbumin (OVA) up to 12 weeks and bronchoalveolar lavage fluid (BALF) and lung tissue collected after the last challenge were evaluated. Chronic OVA challenge induced Gal‐3 expression in the lungs of WT mice. Cell counts in BALF and lung immunohistology demonstrated that eosinophil infiltration in OVA‐challenged Gal‐3 KO mice is significantly reduced compared to WT mice. Also, eotaxin‐1, IL‐2, IL‐4 and TGF‐β expression in these mice was substantially lower than in OVA‐challenged WT mice. Decreased eosinophil recruitment in Gal‐3 KO mice was associated with diminished remodeling of the airways with significantly reduced mucus secretion, sub‐epithelial fibrosis, smooth muscle thickness, and peribronchial angiogenesis. Finally, leukocytes from Gal‐3 KO mice demonstrated decreased trafficking on endothelial adhesion molecules compared to WT cells. Overall, blockade of Gal‐3 in a chronic setting leads to diminished airway inflammation and remodeling potentially due to reduced trafficking of inflammatory cells to sites of inflammation. 1National Institutes of Health grants AI35796, U19‐AI70535, HL0793041.