Allergen-induced airway remodeling is impaired in galectin-3-deficient mice

• Published in: The Journal of immunology (1950) Vol. 185; no. 2; pp. 1205 - 1214
• Main Authors: Ge, Xiao Na, Bahaie, Nooshin S, Kang, Bit Na, Hosseinkhani, M Reza, Ha, Sung Gil, Frenzel, Elizabeth M, Liu, Fu-Tong, Rao, Savita P, Sriramarao, P
• Format: Journal Article
• Language: English
• Published: United States 15-07-2010
• Subjects: Airway Remodeling - genetics; Airway Remodeling - immunology; Allergens - immunology; Animals; Blotting, Western; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - immunology; Chemokine CCL11 - genetics; Chemokine CCL11 - metabolism; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - pathology; Female; Flow Cytometry; Galectin 3 - deficiency; Galectin 3 - genetics; Galectin 3 - immunology; Inflammation - immunology; Interleukin-13 - metabolism; Interleukin-5 - metabolism; Leukocyte Rolling - immunology; Lung - immunology; Lung - metabolism; Lung - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin - immunology; Reverse Transcriptase Polymerase Chain Reaction; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - immunology; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000039

The role played by the beta-galactoside-binding lectin galectin-3 (Gal-3) in airway remodeling, a characteristic feature of asthma that leads to airway dysfunction and poor clinical outcome in humans, was investigated in a murine model of chronic allergic airway inflammation. Wild-type (WT) and Gal-3 knockout (KO) mice were subjected to repetitive allergen challenge with OVA up to 12 wk, and bronchoalveolar lavage fluid (BALF) and lung tissue collected after the last challenge were evaluated for cellular features associated with airway remodeling. Compared to WT mice, chronic OVA challenge in Gal-3 KO mice resulted in diminished remodeling of the airways with significantly reduced mucus secretion, subepithelial fibrosis, smooth muscle thickness, and peribronchial angiogenesis. The higher degree of airway remodeling in WT mice was associated with higher Gal-3 expression in the BALF as well as lung tissue. Cell counts in BALF and lung immunohistology demonstrated that eosinophil infiltration in OVA-challenged Gal-3 KO mice was significantly reduced compared with that WT mice. Evaluation of cellular mediators associated with eosinophil recruitment and airway remodeling revealed that levels of eotaxin-1, IL-5, IL-13, found in inflammatory zone 1, and TGF-beta were substantially lower in Gal-3 KO mice. Finally, leukocytes from Gal-3 KO mice demonstrated decreased trafficking (rolling) on vascular endothelial adhesion molecules compared with that of WT cells. Overall, these studies demonstrate that Gal-3 is an important lectin that promotes airway remodeling via airway recruitment of inflammatory cells, specifically eosinophils, and the development of a Th2 phenotype as well as increased expression of eosinophil-specific chemokines and profibrogenic and angiogenic mediators.