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KMID : 0620920130450060003
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Experimental & Molecular Medicine
2013 Volume.45 No. 6 p.3 ~ p.0
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Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils
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Jung Young-Su
Lee Ha-Young
Kim Sang-Doo
Park Joon-Seong
Kim Jung-Kuk
Suh Pann-Ghill
Bae Yoe-Sik
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Abstract
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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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KEYWORD
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chemotaxis, Gi-protein coupled receptor, neutrophils, Wnt5a
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