Kojima Reiji, Ohno Tatsukuni, Iikura Motoyasu, Niki Toshiro, Hirashima Mitsuomi, Iwaya Keichi, Tsuda Hitoshi, Nonoyama Shigeaki, Matsuda Akio, Saito Hirohisa, Matsumoto Kenji, Nakae Susumu
Department of Basic Pathology, National Defense Medical College, Saitama, Japan ; Department of Pediatrics, National Defense Medical College, Saitama, Japan ; Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
PLoS One. 2014 Jan 20;9(1):e86106. doi: 10.1371/journal.pone.0086106. eCollection 2014.
Galectin-9 (Gal-9), a lectin having a β-galactoside-binding domain, can induce apoptosis of Th1 cells by binding to TIM-3. In addition, Gal-9 inhibits IgE/Ag-mediated degranulation of mast cell/basophilic cell lines by binding to IgE, thus blocking IgE/Ag complex formation. However, the role of Gal-9 in mast cell function in the absence of IgE is not fully understood. Here, we found that recombinant Gal-9 directly induced phosphorylation of Erk1/2 but not p38 MAPK in a human mast cell line, HMC-1, which does not express FcεRI. Gal-9 induced apoptosis and inhibited PMA/ionomycin-mediated degranulation of HMC-1 cells. On the other hand, Gal-9 induced cytokine and/or chemokine production by HMC-1 cells, dependent on activation of ERK1/2 but not p38 MAPK. In addition, the lectin activity of Gal-9 was required for Gal-9-mediated cytokine secretion by HMC-1 cells. These observations suggest that Gal-9 has dual properties as both a regulator and an activator of mast cells.
半乳糖凝集素-9（Gal-9）是一种具有β-半乳糖苷结合结构域的凝集素，它可以通过与T细胞免疫球蛋白黏蛋白分子-3（TIM-3）结合来诱导Th1细胞凋亡。此外，Gal-9通过与免疫球蛋白E（IgE）结合来抑制IgE/抗原介导的肥大细胞/嗜碱性细胞系的脱颗粒，从而阻止IgE/抗原复合物的形成。然而，Gal-9在无IgE情况下对肥大细胞功能的作用尚未完全明确。在此，我们发现重组Gal-9可直接诱导人肥大细胞系HMC-1中细胞外信号调节激酶1/2（Erk1/2）的磷酸化，但不诱导p38丝裂原活化蛋白激酶（p38 MAPK）的磷酸化，HMC-1细胞不表达高亲和力IgE受体（FcεRI）。Gal-9可诱导HMC-1细胞凋亡并抑制佛波酯（PMA）/离子霉素介导的HMC-1细胞脱颗粒。另一方面，Gal-9可诱导HMC-1细胞产生细胞因子和/或趋化因子，这依赖于Erk1/2而非p38 MAPK的激活。此外，Gal-9的凝集素活性是HMC-1细胞分泌Gal-9介导的细胞因子所必需的。这些观察结果表明，Gal-9作为肥大细胞的调节剂和激活剂具有双重特性。
