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.
Highlights
Wnts, which are secreted glycoproteins, are reported to be important in the regulation of diversephysiological responses, including cell migration, embryonic development and tissue organization.[1]
Chemotactic effect of Wnt5a on human neutrophils To examine whether human neutrophils express receptors for Wnt5a, we analyzed mRNA for FZD2, 3, 4, 5 and 8 by semiquantitative reverse-transcription PCR
As soluble frizzled related protein-1 (sFRP1) binds to Wnt5a and blocks the action of Wnt5a to its specific receptors,[19] we examined the effect of sFRP1 on Wnt5a-induced human neutrophil chemotaxis
Summary
Wnts, which are secreted glycoproteins, are reported to be important in the regulation of diverse (patho)physiological responses, including cell migration, embryonic development and tissue organization.[1]. Neutrophils, which are first recruited to an infected area or injured site by a chemoattractant gradient, are important in the regulation of the immune response, especially the innate immune response.[7,8] Various extracellular stimuli can activate neutrophils, resulting in the production of several important mediators: inflammatory cytokines and reactive oxygen species.[9,10] It is critical for the host defense mechanism that circulating neutrophils are recruited into an infected or injured area. We investigated whether human neutrophils express Wnt5a receptors, and the function of Wnt5a in neutrophil activity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
