Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils
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- Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils
- Jung, Young Su; Lee, Ha Young; Kim, Sang Doo; Park, Joon Seong; Kim, Jung Kuk; Suh, Pann-Ghill; Bae, Yoe-Sik
- Chemotaxis; Gi-protein coupled receptor; Neutrophils; Wnt5a
- Issue Date
- NATURE PUBLISHING GROUP
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.45, no.6, pp.1 - 8
- 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.
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