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Galectin-9 Inhibits CD44–Hyaluronan Interaction and Suppresses a Murine Model of Allergic Asthma

2007; American Thoracic Society; Volume: 176; Issue: 1 Linguagem: Inglês

10.1164/rccm.200608-1243oc

1535-4970

Shigeki Katoh, Naoki Ishii, Atsuya Nobumoto, Keisuke Takeshita, Shuyan Dai, Rika Shinonaga, Toshiro Niki, Nozomu Nishi, Akira Tominaga, Akira Yamauchi, Mitsuomi Hirashima,

Invertebrate Immune Response Mechanisms

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.We evaluated the effect of a stable form of the human protein on allergic airway inflammation in a mite allergen-induced asthma model.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.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.We conclude that Gal-9 inhibits allergic inflammation of the airway and AHR by modulating CD44-dependent leukocyte recognition of the extracellular matrix.