Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils.
- Author:
Young Su JUNG
1
;
Ha Young LEE
;
Sang Doo KIM
;
Joon Seong PARK
;
Jung Kuk KIM
;
Pann Ghill SUH
;
Yoe Sik BAE
Author Information
1. Department of Biological Science, Sungkyunkwan University, Suwon, South Korea. yoesik@skku.edu
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
chemotaxis;
Gi-protein coupled receptor;
neutrophils;
Wnt5a
- MeSH:
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/metabolism;
Mice;
NF-kappa B/metabolism;
Neutrophils/*cytology/drug effects/enzymology/*metabolism;
Pertussis Toxin/pharmacology;
Phosphatidylinositol 3-Kinases/metabolism;
Proto-Oncogene Proteins c-akt/metabolism;
Receptors, Wnt/metabolism;
Type C Phospholipases/metabolism;
Wnt Proteins/*pharmacology;
p38 Mitogen-Activated Protein Kinases/metabolism
- From:Experimental & Molecular Medicine
2013;45(6):e27-
- CountryRepublic of Korea
- Language:English
-
Abstract:
Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (beta-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.
