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

Abstract

Galectin-3 is a member of a beta-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.

• Authors: 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
• Journal: The American journal of pathology (Am J Pathol) Vol. 165 Issue 6 Pg. 2045-53 (Dec 2004) ISSN: 0002-9440 [Print] United States
• PMID: 15579447 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytokines
• Galectin 3
• RNA, Messenger
• Immunoglobulin E
• Ovalbumin

Topics

• Animals
• Asthma (metabolism, pathology)
• Bronchial Hyperreactivity (etiology, metabolism)
• Bronchoalveolar Lavage Fluid
• Cells, Cultured
• Cytokines (metabolism)
• Disease Models, Animal
• Eosinophils (immunology, pathology)
• Female
• Galectin 3 (physiology)
• Immunization
• Immunoglobulin E (pharmacology)
• Macrophages (immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Ovalbumin (administration & dosage)
• RNA, Messenger (metabolism)
• Th1 Cells (immunology)
• Th2 Cells (immunology)