Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils

• Published in: Experimental & molecular medicine 2013-06, Vol.45 (6), p.e27-e27
• Main Authors: Su Jung, Young, Young Lee, Ha, Doo Kim, Sang, Seong Park, Joon, Kuk Kim, Jung, Suh, Pann-Ghill, Bae, Yoe-Sik
• Format: Article
• Language: English
• Subjects: Activating Transcription Factor 2 - metabolism; Animals; Biomedical and Life Sciences; Biomedicine; Cell Separation; Chemokines - biosynthesis; Chemotaxis - drug effects; Culture Media, Conditioned - pharmacology; Extracellular Signal-Regulated MAP Kinases - metabolism; GTP-Binding Proteins - metabolism; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Medical Biochemistry; Mice; Molecular Medicine; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - enzymology; Neutrophils - metabolism; NF-kappa B - metabolism; Original; original-article; p38 Mitogen-Activated Protein Kinases - metabolism; Pertussis Toxin - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Receptors, Wnt - metabolism; Stem Cells; Type C Phospholipases - metabolism; Wnt Proteins - pharmacology; Wnt-5a Protein
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/emm.2013.48

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. Immunity: A call to arms A factor secreted by ‘early responder’ immune cells stimulates a signaling loop that fuels the initial response against infection. These cells belong to the innate immune system, which is the first line of defense and releases diverse signaling molecules to recruit other immune cells against invading pathogens. Researchers led by Yoe-Sik Bae of Sungkyunkwan University in South Korea have demonstrated that an immunostimulatory protein called Wnt5a promotes this initial immune migration. Cells called macrophages ‘consume’ the pathogens they encounter, and subsequently alert other cells by producing Wnt5a and other signals. The researchers showed that Wnt5a in turn attracts innate immune cells known as neutrophils, and triggers multiple signaling cascades in these cells. This causes them to secrete additional signals that attract more neutrophils and other immune cell types, thereby strengthening protection against bacteria and viruses.