Human Galectin-3 Is a Novel Chemoattractant for Monocytes and Macrophages

• Published in: The Journal of immunology (1950) Vol. 165; no. 4; pp. 2156 - 2164
• Main Authors: Sano, Hideki, Hsu, Daniel K, Yu, Lan, Apgar, John R, Kuwabara, Ichiro, Yamanaka, Tohru, Hirashima, Mitsuomi, Liu, Fu-Tong
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-08-2000
• Subjects: Animals; Antigens, Differentiation - administration & dosage; Antigens, Differentiation - metabolism; Antigens, Differentiation - physiology; Calcium - metabolism; Cell Migration Inhibition; Cell Movement - immunology; Cells, Cultured; Chemokine CCL2 - physiology; Chemotactic Factors - administration & dosage; Chemotactic Factors - metabolism; Chemotactic Factors - physiology; Chemotaxis, Leukocyte - immunology; Diffusion Chambers, Culture; Dose-Response Relationship, Immunologic; Galectin 3; Humans; Injections, Intradermal; Intracellular Fluid - metabolism; Kinetics; Macrophages - immunology; Macrophages, Alveolar - immunology; Mice; Mice, Inbred BALB C; Monocytes - immunology; Monocytes - metabolism; Monocytes - pathology; Pertussis Toxin; Protein Structure, Tertiary; Receptors, Chemokine - physiology; Signal Transduction - immunology; Skin - immunology; Skin - pathology; Virulence Factors, Bordetella - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.4.2156

Galectin-3 is a beta-galactoside-binding protein implicated in diverse biological processes. We found that galectin-3 induced human monocyte migration in vitro in a dose-dependent manner, and it was chemotactic at high concentrations (1.0 microM) but chemokinetic at low concentrations (10-100 nM). Galectin-3-induced monocyte migration was inhibited by its specific mAb and was blocked by lactose and a C-terminal domain fragment of the protein, indicating that both the N-terminal and C-terminal domains of galectin-3 are involved in this activity. Pertussis toxin (PTX) almost completely blocked monocyte migration induced by high concentrations of galectin-3. Galectin-3 caused a Ca2+ influx in monocytes at high, but not low, concentrations, and both lactose and PTX inhibited this response. There was no cross-desensitization between galectin-3 and any of the monocyte-reactive chemokines examined, including monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, and stromal cell-derived factor-1alpha. Cultured human macrophages and alveolar macrophages also migrated toward galectin-3, but not monocyte chemotactic protein-1. Finally, galectin-3 was found to cause monocyte accumulation in vivo in mouse air pouches. These results indicate that galectin-3 is a novel chemoattractant for monocytes and macrophages and suggest that the effect is mediated at least in part through a PTX-sensitive (G protein-coupled) pathway.