Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils |
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| Authors: | Young Su Jung Ha Young Lee Sang Doo Kim Joon Seong Park Jung Kuk Kim Pann-Ghill Suh Yoe-Sik Bae |
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| Institution: | 1.Department of Biological Science, Sungkyunkwan University, Suwon, South Korea;2.Mitochondria Hub Regulation Center, Dong-A University, Busan, South Korea;3.Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea;4.School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, South Korea;5.Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea. |
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| 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. |
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| Keywords: | chemotaxis Gi-protein coupled receptor neutrophils Wnt5a |
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