Galectin-9 is a high affinity IgE-binding lectin with anti-allergic effect by blocking IgE-antigen complex formation.
Galectin (Gal)-9 was first described as an eosinophil chemoattractant. With the progress in research, Gal-9 has come to be known as a versatile immunomodulator that is involved in various aspects of immune regulations, and the entire picture of the function still remains elusive. To uncover as-yet unknown activity of Gal-9, we have been examining the effect of the protein in various disease animal models. Here we show that Gal-9 attenuated asthmatic reaction in guinea pigs and suppressed passive-cutaneous anaphylaxis in mice. These results indicate the mast cell stabilizing effect of Gal-9. In vitro studies of mast cell degranulation involving RBL-2H3 cells demonstrated that Gal-9 suppressed degranulation from the cells stimulated by IgE plus antigen and that the inhibitory effect was completely abrogated in the presence of lactose, indicating lectin activity of Gal-9 is critical. We found that Gal-9 strongly and specifically bound IgE, which is a heavily glycosylated immunoglobulin, and that the interaction prevented IgE-antigen complex formation, clarifying the mode of action of the anti-degranulation effect. Gal-9 is expressed by several mast cells including mouse mast cell line MC/9. The fact that immunological stimuli of MC/9 cells augmented Gal-9 secretion from the cells implies that Gal-9 is an autocrine regulator of mast cell function to suppress excessive degranulation. Collectively, these findings shed light on a novel function of Gal-9 in mast cells and suggest a beneficial utility of Gal-9 for the treatment of allergic disorders including asthma.
Niki
Toshiro
T
Research Division, GalPharma Company, Ltd., FROM-Kagawa, 2217-16 Hayashi-cho, Takamatsu, Kagawa 761-0301, Japan. niki.t@galpharma.com
Tsutsui
Shoko
S
Hirose
Shigeru
S
Aradono
Sachiko
S
Sugimoto
Yasushi
Y
Takeshita
Keisuke
K
Nishi
Nozomu
N
Hirashima
Mitsuomi
M
D000818:Animals; D000941:Antigens / Q000737:chemistry*; D045744:Cell Line, Tumor; D005260:Female; D037161:Galectins / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry*; D019169:Jurkat Cells; D037102:Lectins / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D051381:Rats; D017455:Receptors, IgE / Q000737:chemistry*
D000941:Antigens; D037161:Galectins; C105032:LGALS9 protein, human; D037102:Lectins; D017455:Receptors, IgE; C508186:galectin 9, mouse; D007073:Immunoglobulin E