Eosinophil-expressed galectin-3 regulates cell trafficking and migration

Abstract

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.

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

“…Involvement of O-versus complex N-glycans in Gal-1-mediated apoptosis was examined by exposing eosinophils cultured in medium containing BG or BM eosinophils from Adhesion and Migration Assays. The effects of Gal-1 on eosinophil adhesion and migration were evaluated as described previously (48,49) and are detailed in SI Materials and Methods.…”

The role of eosinophils and basophils in allergic diseases considering genetic findings

“…Gal-3, a β galactoside binding lectin, is implicated in the pathogenesis of allergic airway inflammation. Gal-3 -/-mice exposed to chronic allergen (OVA) challenge have attenuated airway eosinophilia and exhibit less severe remodeling of the airways [11]. Furthermore, airway eosinophilia in acute and chronic allergen-challenged mice was accompanied with elevated levels of extracellular soluble Gal-3 in the BALF and intracellular Gal-3 in the lung tissue [11].…”

“…Gal-3 -/-mice exposed to chronic allergen (OVA) challenge have attenuated airway eosinophilia and exhibit less severe remodeling of the airways [11]. Furthermore, airway eosinophilia in acute and chronic allergen-challenged mice was accompanied with elevated levels of extracellular soluble Gal-3 in the BALF and intracellular Gal-3 in the lung tissue [11]. Gal-3 is secreted by various cell types such as macrophages and activated Th2 cells, but also by eosinophils especially when exposed to eotaxin-1.…”

Proteomic Analysis in Esophageal Eosinophilia Reveals Differential Galectin-3 Expression and S-Nitrosylation

“…It is important in the generation of Th2-mediated allergic responses, being a part of the IgE complex with FcRεI and CD23. It is abundantly expressed in epithelial, dendritic and T cells and functions as a cell surface adhesion molecule on eosinophils to support cell rolling and adhesion [26,27] . Airway recruitment of eosinophils correlated with increased galectin-3 expression in the lungs [24,28] .…”

“…The most upregulated of these proteins, with increased expression more than 1.5 times normal in PE samples and more than 2 times normal in DE samples, was galectin-3, a galactose-specific lectin that binds IgE and is involved in acute inflammatory responses including activation of mast cells [23] . Of the 4 proteins described above, galectin-3 [24][25][26][27] was confirmed as being differentially expressed by Western blot analysis, with EE inflamed samples being significantly higher than controls ( fig. 2 a-c).…”