Galectin-2 Induces a Proinflammatory, Anti-Arteriogenic Phenotype in Monocytes and Macrophages

被引：48

作者：

Yildirim, Cansu ^{[1
]}

Vogel, Daphne Y. S. ^{[1
]}

Hollander, Maurits R. ^{[2
]}

Baggen, Josefien M. ^{[1
]}

Fontijn, Ruud D. ^{[1
]}

Nieuwenhuis, Sylvia ^{[1
]}

Haverkamp, Anouk ^{[1
]}

de Vries, Margreet R. ^{[3
]}

Quax, Paul H. A. ^{[3
]}

Garcia-Vallejo, Juan J. ^{[1
]}

van der Laan, Anja M. ^{[4
]}

Dijkstra, Christine D. ^{[1
]}

Kraan, Tineke C. T. M. van der Pouw ^{[1
]}

van Royen, Niels ^{[2
]}

Horrevoets, Anton J. G. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol & Immunol, Amsterdam, Netherlands

[2] Vrije Univ Amsterdam, Med Ctr, Dept Cardiol, Amsterdam, Netherlands

[3] Leiden Univ, Med Ctr, Einthoven Labs, Dept Vasc Surg, Leiden, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands

来源：

PLOS ONE | 2015年 / 10卷 / 04期

关键词：

GROWTH FACTOR-A; FACTOR-B; POLARIZATION; MECHANISMS; ROLES; ANGIOGENESIS; STIMULATION; ACTIVATION; EXPRESSION; MOLECULES;

D O I：

10.1371/journal.pone.0124347

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：20

共 49 条

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