Galectin-9 Is a High Affinity IgE-binding Lectin with Anti-allergic Effect by Blocking IgE-Antigen Complex Formation
Galectin-9 Is a High Affinity IgE-binding Lectin with Anti-allergic Effect by Blocking IgE-Antigen Complex Formation
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DOI：
10.1074/jbc.m109.035196
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发表时间：
2009-11-20
影响因子：
4.8
通讯作者：
Hirashima, Mitsuomi
中科院分区：
文献类型：
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作者：
Niki, Toshiro;Tsutsui, Shoko;Hirashima, Mitsuomi
半乳糖凝集素（Gal）-9首先被描述为嗜酸性粒细胞化学引诱物。随着研究的进展，Gal-9已被认为是一种多功能的免疫调节剂，参与免疫调节的各个方面，其功能的全貌仍然是难以捉摸的。为了揭示Gal-9的未知活性，我们一直在研究该蛋白质在各种疾病动物模型中的作用。在这里，我们表明Gal-9减弱豚鼠的哮喘反应和抑制小鼠的被动皮肤过敏反应。这些结果表明Gal-9的肥大细胞稳定作用。涉及RBL-2 H3细胞的肥大细胞脱颗粒的体外研究表明，Gal-9抑制由IgE加抗原刺激的细胞的脱颗粒，并且在乳糖的存在下抑制作用完全消除，表明Gal-9的凝集素活性是关键的。我们发现，Gal-9强烈和特异性地结合IgE，这是一种高度糖基化的免疫球蛋白，并且这种相互作用阻止了IgE-抗原复合物的形成，阐明了抗脱粒作用的作用模式。Gal-9由包括小鼠肥大细胞系MC/9的几种肥大细胞表达。MC/9细胞的免疫刺激增加了Gal-9从细胞中分泌的事实意味着Gal-9是肥大细胞功能的自分泌调节剂，以抑制过度脱粒。总的来说，这些发现揭示了Gal-9在肥大细胞中的新功能，并表明Gal-9用于治疗包括哮喘在内的过敏性疾病的有益用途。
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.