Critical Role for Galectin-3 in Airway Inflammation and Bronchial Hyperresponsiveness in a Murine Model of Asthma

• Published in: The American journal of pathology Vol. 165; no. 6; pp. 2045 - 2053
• Main Authors: Zuberi, Riaz I., Hsu, Daniel K., Kalayci, Omer, Chen, Huan-Yuan, Sheldon, Holly K., Yu, Lan, Apgar, John R., Kawakami, Toshiaki, Lilly, Craig M., Liu, Fu-Tong
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01-12-2004; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Asthma - metabolism; Asthma - pathology; Biological and medical sciences; Bronchial Hyperreactivity - etiology; Bronchial Hyperreactivity - metabolism; Bronchoalveolar Lavage Fluid; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; Cytokines - metabolism; Disease Models, Animal; Eosinophils - immunology; Eosinophils - pathology; Female; Galectin 3 - physiology; Immunization; Immunoglobulin E - pharmacology; Investigative techniques, diagnostic techniques (general aspects); Macrophages - immunology; Macrophages - pathology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Original Research Paper; Ovalbumin - administration & dosage; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pneumology; RNA, Messenger - metabolism; Th1 Cells - immunology; Th2 Cells - immunology; Respiratory tract; Lung disease; Animal model; Anatomic pathology; Hyperreactivity; Respiratory disease; Galectin 3; Bronchus disease; Inflammation; Obstructive pulmonary disease; Respiratory system; Asthma
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)63255-5

Galectin-3 is a member of a β-galactoside-binding animal lectin family. Previous
in vitro
studies have demonstrated that galectin-3 is involved in a number of activities; however, the roles of this lectin in physiological and pathological processes
in vivo
remain to be elucidated. Herein, we show, in a murine model of ovalbumin (OVA)-induced asthma that 1) peribronchial inflammatory cells expressed large amounts of galectin-3; 2) bronchoalveolar lavage fluid from OVA-challenged mice contained significantly higher levels of galectin-3 compared to control mice; and 3) macrophages in bronchoalveolar lavage fluid were the major cell type that contained galectin-3. We investigated the role of galectin-3 in the allergic airway response by comparing galectin-3-deficient (gal3
−/−) mice and wild-type (gal3
+/+) mice. OVA-sensitized gal3
−/− mice developed fewer eosinophils and lower goblet cell metaplasia, after airway OVA challenge compared to similarly treated gal3
+/+ mice. In addition, the OVA-sensitized gal3
−/− mice developed significantly less airway hyperresponsiveness after airway OVA challenge compared to gal3
+/+ mice. Finally, gal3
−/− mice developed a lower Th2 response, but a higher Th1 response, suggesting that galectin-3 regulates the Th1/Th2 response. We conclude that galectin-3 may play an important role in the pathogenesis of asthma and inhibitors of this lectin may prove useful for treatment of this disease.