Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils

Exp Mol Med. 2013 Jun 14;45(6):e27. doi: 10.1038/emm.2013.48.

Abstract

Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (β-catenin-independent pathways). Human neutrophils expressed several Wnt5a receptors, such as Frizzled 2, 5 and 8. Stimulation of human neutrophils with Wnt5a caused chemotactic migration and the production of two important chemokines, CXCL8 and CCL2. CCL2 production by Wnt5a was mediated by a pertussis toxin-sensitive G-protein-dependent pathway. Wnt5a also stimulated the phosphorylation of three mitogen-activated protein kinases (MAPKs: ERK, p38 MAPK and JNK) and Akt. Inhibition of ERK, p38 MAPK or JNK by specific inhibitors induced a dramatic reduction in Wnt5a-induced CCL2 production. Supernatant collected from lipopolysaccharide-stimulated macrophages induced neutrophil chemotaxis, which was significantly inhibited by anti-Wnt5a antibody. Our results suggested that Wnt5a may contribute to neutrophil recruitment, mediating the inflammation response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2 / metabolism
  • Animals
  • Cell Separation
  • Chemokines / biosynthesis*
  • Chemotaxis / drug effects*
  • Culture Media, Conditioned / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • GTP-Binding Proteins / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Neutrophils / cytology*
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Neutrophils / metabolism*
  • Pertussis Toxin / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Wnt / metabolism
  • Type C Phospholipases / metabolism
  • Wnt Proteins / pharmacology*
  • Wnt-5a Protein
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • ATF2 protein, human
  • Activating Transcription Factor 2
  • Chemokines
  • Culture Media, Conditioned
  • Lipopolysaccharides
  • NF-kappa B
  • Receptors, Wnt
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • Pertussis Toxin
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • GTP-Binding Proteins