Eosinophil-expressed galectin-3 regulates cell trafficking and migration

Xiao Na Ge, Sung Gil Ha, Fu-Tong Liu, Savita P. Rao, P. Sriramarao

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberArticle 37
JournalFrontiers in Pharmacology
Volume4 APR
DOIs
StatePublished - 2013

Fingerprint

Galectin 3
Eosinophils
Cell Movement
Chemokine CCL11
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Inflammation
Allergens
Bone Marrow
Galactosides
Lung

Keywords

  • Allergic airway inflammation
  • Cell trafficking
  • Eosinophils
  • Galectin-3
  • Migration

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Ge, X. N., Ha, S. G., Liu, F-T., Rao, S. P., & Sriramarao, P. (2013). Eosinophil-expressed galectin-3 regulates cell trafficking and migration. Frontiers in Pharmacology, 4 APR, [Article 37]. https://doi.org/10.3389/fphar.2013.00037

Eosinophil-expressed galectin-3 regulates cell trafficking and migration. / Ge, Xiao Na; Ha, Sung Gil; Liu, Fu-Tong; Rao, Savita P.; Sriramarao, P.

In: Frontiers in Pharmacology, Vol. 4 APR, Article 37, 2013.

Research output: Contribution to journalArticle

Ge, Xiao Na ; Ha, Sung Gil ; Liu, Fu-Tong ; Rao, Savita P. ; Sriramarao, P. / Eosinophil-expressed galectin-3 regulates cell trafficking and migration. In: Frontiers in Pharmacology. 2013 ; Vol. 4 APR.
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AB - 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.

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