Department of Veterinary and Biomedical Sciences, University of Minnesota St. Paul, MN, USA.
Front Pharmacol. 2013 Apr 5;4:37. doi: 10.3389/fphar.2013.00037. eCollection 2013.
Galectin-3 (Gal-3), a β galactoside-binding lectin, is implicated in the pathogenesis of allergic airway inflammation and allergen-challenged mice deficient in Gal-3 (Gal-3(-/-)) exhibit decreased airway recruitment of eosinophils (Eos). Gal-3 is expressed and secreted by several cell types and can thus function extracellularly and intracellularly to regulate a variety of cellular responses. We sought to determine the role of Eos-expressed Gal-3 in promoting Eos trafficking and migration in the context of allergic airway inflammation using bone marrow (BM)-derived Eos from wild-type (WT) and Gal-3(-/-) mice. Airway recruitment of Eos in acute (4 weeks) and chronic (8-12 weeks) allergen-challenged WT mice correlated with Gal-3 expression in the lungs. BM-derived Eos were found to express Gal-3 on the cell surface and secrete soluble Gal-3 when exposed to eotaxin-1. Compared to WT Eos, Gal-3(-/-) Eos exhibited significantly reduced rolling on vascular cell adhesion molecule 1 (VCAM-1) and decreased stable adhesion on intercellular adhesion molecule 1 (ICAM-1) under conditions of flow in vitro. Evaluation of cytoskeletal rearrangement demonstrated that relatively fewer adherent Gal-3(-/-) Eos undergo cell spreading and formation of membrane protrusions. In addition, cell surface expression of integrin receptor αM (CD11b) was lower in Gal-3(-/-) Eos, which is likely to account for their altered adhesive interactions with VCAM-1 and ICAM-1. Gal-3(-/-) Eos also exhibited significantly decreased migration toward eotaxin-1 compared to WT Eos irrespective of similar levels of CCR3 expression. Further, eotaxin-induced migration of WT Eos remained unaffected in the presence of lactose, suggesting a role for intracellular Gal-3 in regulating Eos migration. Overall, our findings indicate that Gal-3 expression in the lungs correlates with Eos mobilization during allergic airway inflammation and signaling involving intracellular Gal-3 and/or secreted Gal-3 bound to the cell surface of Eos appears to be essential for Eos trafficking under flow as well as for migration.
半乳糖凝集素-3（Gal-3）是一种β半乳糖苷结合凝集素，与过敏性气道炎症的发病机制有关，用过敏原刺激缺乏 Gal-3（Gal-3(-/-)）的小鼠，可观察到气道中嗜酸性粒细胞（Eos）的募集减少。Gal-3 由几种细胞类型表达和分泌，因此可以在细胞外和细胞内发挥作用，调节各种细胞反应。我们试图确定在过敏性气道炎症的背景下，Eos 表达的 Gal-3 在促进 Eos 转运和迁移中的作用，为此我们使用来自野生型（WT）和 Gal-3(-/-) 小鼠的骨髓（BM）衍生的 Eos。急性（4 周）和慢性（8-12 周）过敏原刺激 WT 小鼠气道中 Eos 的募集与肺部的 Gal-3 表达相关。研究发现，BM 衍生的 Eos 在暴露于趋化因子 eotaxin-1 时，在细胞表面表达 Gal-3 并分泌可溶性 Gal-3。与 WT Eos 相比，Gal-3(-/-) Eos 在体外流动条件下，滚动到血管细胞粘附分子 1（VCAM-1）的能力明显降低，稳定粘附到细胞间粘附分子 1（ICAM-1）的能力也降低。细胞骨架重排的评估表明，相对较少的粘附 Gal-3(-/-) Eos 发生细胞扩散并形成膜突起。此外，Gal-3(-/-) Eos 上整合素受体 αM（CD11b）的表面表达较低，这可能是其与 VCAM-1 和 ICAM-1 改变的粘附相互作用的原因。Gal-3(-/-) Eos 向 eotaxin-1 的迁移也明显低于 WT Eos，而 CCR3 表达水平相似。此外，在乳糖存在的情况下，WT Eos 诱导的 eotaxin 迁移不受影响，这表明细胞内 Gal-3 在调节 Eos 迁移中起作用。总体而言，我们的研究结果表明，肺部的 Gal-3 表达与过敏性气道炎症期间 Eos 的动员有关，涉及细胞内 Gal-3 和/或与 Eos 细胞表面结合的分泌型 Gal-3 的信号转导对于在流动状态下的 Eos 转运以及迁移是必需的。
