Regulation of alternative macrophage activation by galectin-3

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternative macrophage activation in bone marrow-derived macrophages in vitro and in resident lung and recruited peritoneal macrophages in vivo without affecting IFN-gamma/LPS-induced classical activation or IL-10-induced deactivation. IL-4-mediated alternative macrophage activation is inhibited by siRNA-targeted deletion of galectin-3 or its membrane receptor CD98 and by inhibition of PI3K. Increased galectin-3 expression and secretion is a feature of alternative macrophage activation. IL-4 stimulates galectin-3 expression and release in parallel with other phenotypic markers of alternative macrophage activation. By contrast, classical macrophage activation with LPS inhibits galectin-3 expression and release. Galectin-3 binds to CD98, and exogenous galectin-3 or cross-linking CD98 with the mAb 4F2 stimulates PI3K activation and alternative activation. IL-4-induced alternative activation is blocked by bis-(3-deoxy-3-(3-methoxybenzamido)-beta-D-galactopyranosyl) sulfane, a specific inhibitor of extracellular galectin-3 carbohydrate binding. These results demonstrate that a galectin-3 feedback loop drives alternative macrophage activation. Pharmacological modulation of galectin-3 function represents a novel therapeutic strategy in pathologies associated with alternatively activated macrophages.


  • Alison C MacKinnon
  • Sarah L Farnworth
  • Philip S Hodkinson
  • Neil C Henderson
  • Kirsten M Atkinson
  • Hakon Leffler
  • Ulf Nilsson
  • Christopher Haslett
  • Stuart J Forbes
  • Tariq Sethi
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Sidor (från-till)2650-2658
TidskriftJournal of Immunology
Utgåva nummer4
StatusPublished - 2008
Peer review utfördJa