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
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 2 / metabolism
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Animals
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Cell Separation
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Chemokines / biosynthesis*
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Chemotaxis / drug effects*
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Culture Media, Conditioned / pharmacology
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Extracellular Signal-Regulated MAP Kinases / metabolism
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GTP-Binding Proteins / metabolism
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects
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Macrophages / metabolism
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Mice
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NF-kappa B / metabolism
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Neutrophils / cytology*
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Neutrophils / drug effects
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Neutrophils / enzymology
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Neutrophils / metabolism*
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Pertussis Toxin / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Proto-Oncogene Proteins c-akt / metabolism
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Receptors, Wnt / metabolism
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Type C Phospholipases / metabolism
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Wnt Proteins / pharmacology*
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Wnt-5a Protein
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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ATF2 protein, human
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Activating Transcription Factor 2
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Chemokines
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Culture Media, Conditioned
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Lipopolysaccharides
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NF-kappa B
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Receptors, Wnt
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Wnt Proteins
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Wnt-5a Protein
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Wnt5a protein, mouse
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Pertussis Toxin
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Type C Phospholipases
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GTP-Binding Proteins