Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma

Riaz I. Zuberi, Daniel K. Hsu, Omer Kalayci, Huan Yuan Chen, Holly K. Sheldon, Lan Yu, John R. Apgar, Toshiaki Kawakami, Craig M. Lilly, Fu-Tong Liu

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131 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2045-2053
Number of pages9
JournalAmerican Journal of Pathology
Volume165
Issue number6
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Zuberi, R. I., Hsu, D. K., Kalayci, O., Chen, H. Y., Sheldon, H. K., Yu, L., Apgar, J. R., Kawakami, T., Lilly, C. M., & Liu, F-T. (2004). Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma. American Journal of Pathology, 165(6), 2045-2053.