Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of allergic asthma.
BACKGROUND
Galectin-9 (Gal-9) belongs to the galectin family, which exhibits affinity for beta-galactosides. Gal-9 has a variety of biological activities; however, its role in allergic inflammation is unknown.


OBJECTIVE
We evaluated the effect of a stable form of the human protein on allergic airway inflammation in a mite allergen-induced asthma model.


METHODS
Human stable Gal-9 was given by intravenous injection to mice during antigen challenge. The effect of Gal-9 on airway inflammation and airway hyperresponsiveness (AHR) was then evaluated.


RESULTS
Gal-9 reduced AHR as well as Th2-associated airway inflammation. Furthermore, administration of Gal-9 as well as anti-CD44 monoclonal antibody inhibited the infiltration of peripheral blood Th2 cells into the airway. Interestingly, Gal-9 directly bound the CD44 adhesion molecule and inhibited interactions with hyaluronan (HA). Consistent with the concept that CD44-HA interactions mediate the migration of T cells into the lung, Gal-9 blocked CD44-dependent adhesion of BW5147 mouse T cells to HA.


CONCLUSIONS
We conclude that Gal-9 inhibits allergic inflammation of the airway and AHR by modulating CD44-dependent leukocyte recognition of the extracellular matrix.
Katoh
Shigeki
S
Department of Cell Regulation, Faculty of Medicine, Kagawa University, Kagawa, Japan. kshigeki@med.kagawa-u.ac.jp
Ishii
Naoki
N
Nobumoto
Atsuya
A
Takeshita
Keisuke
K
Dai
Shu-Yan
SY
Shinonaga
Rika
R
Niki
Toshiro
T
Nishi
Nozomu
N
Tominaga
Akira
A
Yamauchi
Akira
A
Hirashima
Mitsuomi
M
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods; D003546:Cysteine Endopeptidases; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000276:immunology; D037161:Galectins / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D006820:Hyaluronic Acid / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D037161:Galectins; D018960:Hyaluronan Receptors; C105032:LGALS9 protein, human; D006820:Hyaluronic Acid; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1