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.
Highlights
Galectins (1–15) are members of a highly conserved family of animal lectins defined by their affinity for β-galactose-containing oligosaccharides (Liu et al, 2012a)
AIRWAY EOSINOPHILIA IN ALLERGEN-CHALLENGED MICE IS ASSOCIATED WITH ELEVATED Gal-3 EXPRESSION IN THE LUNGS Differential cell counts in broncho alveolar lavage fluid (BALF) of acute or chronic allergenexposed mice indicated increased recruitment of Eos compared with control mice
Relative to WT mice, development of allergen-induced airway eosinophilia, inflammation, airway hyperresponsiveness (AHR), and remodeling were all significantly attenuated in mice that were deficient in Gal-3
Summary
Galectins (1–15) are members of a highly conserved family of animal lectins defined by their affinity for β-galactose-containing oligosaccharides (Liu et al, 2012a). They do not contain a classical signal sequence nor a transmembrane domain and are located intracellularly (cytoplasm and nucleus), but are present extracellularly (Ochieng et al, 1993; Hughes, 1999; Leffler, 2001). Previous studies have implicated a role for endogenous Gal in the pathogenesis of allergic airway inflammation. In vivo studies have demonstrated that Gal-3 expression in the lungs is upregulated during allergic asthma and Gal-3 deficient (Gal-3−/−)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
