Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma.
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.
Zuberi
Riaz I
RI
Division of Allergy, La Jolla Institute of Allergy and Immunology, San Diego, California, USA.
Hsu
Daniel K
DK
Kalayci
Omer
O
Chen
Huan-Yuan
HY
Sheldon
Holly K
HK
Yu
Lan
L
Apgar
John R
JR
Kawakami
Toshiaki
T
Lilly
Craig M
CM
Liu
Fu-Tong
FT
D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005260:Female; D037502:Galectin 3 / Q000502:physiology*; D007114:Immunization; D007073:Immunoglobulin E / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D037502:Galectin 3; D012333:RNA, Messenger; D007073:Immunoglobulin E; D010047:Ovalbumin