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

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51 Citations (Scopus)

Abstract

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
Original languageEnglish
Article numbere0124347
Pages (from-to)e0124347
JournalPLOS ONE
Volume10
Issue number4
DOIs
Publication statusPublished - 2015

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