PLoS ONE (Jan 2015)

Galectin-2 induces a proinflammatory, anti-arteriogenic phenotype in monocytes and macrophages.

  • Cansu Yıldırım,
  • Daphne Y S Vogel,
  • Maurits R Hollander,
  • Josefien M Baggen,
  • Ruud D Fontijn,
  • Sylvia Nieuwenhuis,
  • Anouk Haverkamp,
  • Margreet R de Vries,
  • Paul H A Quax,
  • Juan J Garcia-Vallejo,
  • Anja M van der Laan,
  • Christine D Dijkstra,
  • Tineke C T M van der Pouw Kraan,
  • Niels van Royen,
  • Anton J G Horrevoets

DOI
https://doi.org/10.1371/journal.pone.0124347
Journal volume & issue
Vol. 10, no. 4
p. e0124347

Abstract

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Galectin-2 is a monocyte-expressed carbohydrate-binding lectin, for which increased expression is genetically determined and associated with decreased collateral arteriogenesis in obstructive coronary artery disease patients. The inhibiting effect of galectin-2 on arteriogenesis was confirmed in vivo, but the mechanism is largely unknown. In this study we aimed to explore the effects of galectin-2 on monocyte/macrophage phenotype in vitro and vivo, and to identify the receptor by which galectin-2 exerts these effects. We now show that the binding of galectin-2 to different circulating human monocyte subsets is dependent on monocyte surface expression levels of CD14. The high affinity binding is blocked by an anti-CD14 antibody but not by carbohydrates, indicating a specific protein-protein interaction. Galectin-2 binding to human monocytes modulated their transcriptome by inducing proinflammatory cytokines and inhibiting pro-arteriogenic factors, while attenuating monocyte migration. Using specific knock-out mice, we show that galectin-2 acts through the CD14/toll-like receptor (TLR)-4 pathway. Furthermore, galectin-2 skews human macrophages to a M1-like proinflammatory phenotype, characterized by a reduced motility and expression of an anti-arteriogenic cytokine/growth factor repertoire. This is accompanied by a switch in surface protein expression to CD40-high and CD206-low (M1). In a murine model we show that galectin-2 administration, known to attenuate arteriogenesis, leads to increased numbers of CD40-positive (M1) and reduced numbers of CD206-positive (M2) macrophages surrounding actively remodeling collateral arteries. In conclusion galectin-2 is the first endogenous CD14/TLR4 ligand that induces a proinflammatory, non-arteriogenic phenotype in monocytes/macrophages. Interference with CD14-Galectin-2 interaction may provide a new intervention strategy to stimulate growth of collateral arteries in genetically compromised cardiovascular patients.