Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of allergic asthma.

Abstract

RATIONALE 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. OBJECTIVES 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. MEASUREMENTS AND MAIN 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.

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@article{Katoh2007Galectin9IC, title={Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of allergic asthma.}, author={Shigeki Katoh and Naoki Ishii and Atsuya Nobumoto and Keisuke Takeshita and Shu-Yan Dai and Rika Shinonaga and Toshiro Niki and Nozomu Nishi and A. Tominaga and Akira Yamauchi and Mitsuomi Hirashima}, journal={American journal of respiratory and critical care medicine}, year={2007}, volume={176 1}, pages={27-35} }