title: Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils.
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.
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, South Korea [2] Mitochondria Hub Regulation Center, Dong-A University, Busan, South Korea.
authors.forename: Young Su
authors.initials: YS
authors.lastname: Jung
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Sang Doo
authors.initials: SD
authors.lastname: Kim
authors.forename: Joon Seong
authors.initials: JS
authors.lastname: Park
authors.forename: Jung Kuk
authors.initials: JK
authors.lastname: Kim
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism; D000818:Animals; D002469:Cell Separation; D018925:Chemokines / Q000096:biosynthesis*; D002633:Chemotaxis / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060490:Receptors, Wnt / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D051153:Wnt Proteins / Q000494:pharmacology*; D000071818:Wnt-5a Protein; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D018925:Chemokines; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D016328:NF-kappa B; D060490:Receptors, Wnt; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins