Human galectin-3 is a novel chemoattractant for monocytes and macrophages.
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.
Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
H
H
Sano
D K
DK
Hsu
L
L
Yu
J R
JR
Apgar
I
I
Kuwabara
T
T
Yamanaka
M
M
Hirashima
F T
FT
Liu
D000818:Animals; D000943:Antigens, Differentiation / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000502:physiology; D002630:Chemotactic Factors / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D015194:Diffusion Chambers, Culture; D004306:Dose-Response Relationship, Immunologic; D037502:Galectin 3; D006801:Humans; D007271:Injections, Intradermal; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D037342:Pertussis Toxin; D017434:Protein Structure, Tertiary; D019707:Receptors, Chemokine / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000943:Antigens, Differentiation; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D037502:Galectin 3; D019707:Receptors, Chemokine; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D002118:Calcium