Galectin-9 in allergic airway inflammation and hyper-responsiveness in mice.
BACKGROUND
Galectin-9 (Gal-9) is a member of the growing family of beta-galactoside-binding lectins. Gal-9 is an eosinophil chemoattractant and inducer of Th1 cell apoptosis. These effects suggest its potential role in the pathogenesis of asthma. Our aim was to study the expression of Gal-9 in an ovalbumin (OVA)-induced mouse model of allergic asthma.


METHODS
To investigate the significance of Gal-9 in allergic inflammation and airway hyperresponsiveness (AHR), a group of BALB/c mice was sensitized and challenged with OVA (G(OVA)). Another group of animals was allergized with OVA and also treated with dexamethasone (DEX) (G(OVA+DEX)). The control group (G(PBS)) received phosphate-buffered saline instead of OVA as placebo. Airway reactivity to intravenous methacholine was assessed.


RESULTS
The percentage of Gal-9-positive cells and their intracellular Gal-9 content and Th1/Th2 cytokine levels in the bronchoalveolar lavage (BAL) were determined by flow cytometry. Gal-9 mRNA expression and protein level were measured in the lung tissue by real-time RT-PCR and Western blot. In G(OVA )mice, airway inflammation and mucus hypersecretion developed. DEX treatment inhibited the main features of experimental asthma. The number of Gal-9-positive lymphocytes, eosinophil and neutrophil granulocytes and the levels of Th2 cytokines were higher in the BAL of G(OVA) compared to G(PBS) or G(OVA+DEX )mice. Moreover, Gal-9 protein level was elevated in the lungs of G(OVA) mice.


CONCLUSIONS
These results suggest that Gal-9 plays a role as a mediator contributing to the development of allergic airway inflammation. Gal-9 may serve as a recruiter of eosinophil granulocytes and promoter of Th2 dominance.
First Department of Pediatrics, Semmelweis University, Budapest, Hungary. sziksz@gyer1.sote.hu
Erna
E
Sziksz
Gergely Tibor
GT
Kozma
Eva
E
Pállinger
Zsolt István
ZI
Komlósi
Csaba
C
Adori
Lajos
L
Kovács
Beáta
B
Szebeni
Krisztina
K
Rusai
György
G
Losonczy
András
A
Szabó
Adám
A
Vannay
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D037161:Galectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010047:Ovalbumin / Q000276:immunology*; D012129:Respiratory Function Tests
D000485:Allergens; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D037161:Galectins; C508186:galectin 9, mouse; D016210:Methacholine Chloride; D003907:Dexamethasone; D010047:Ovalbumin