EMR2 Receptor Ligation Modulates Cytokine Secretion Profiles and Cell Survival of Lipopolysaccharide-treated Neutrophils

Background: Epidermal growth factor (EGF)-like module-containing mucin-like hormonereceptor-like 2 (EMR2) is an adhesion G protein-coupled receptor previouslyshown to potentiate neutrophil responses to a number of inflammatory stimuli. EMR2 activation promotes neutrophil adhesion and migration, and augments production of reactive oxygen species and degranulation. In this study,we examined the effect of EMR2 ligation by its specific antibody on thecytokine expression profile and cell survival of lipopolysaccharide (LPS)-treated neutrophils.Methods: Neutrophils were treated with LPS in the absence or presence of the antiEMR2 mAb, 2A1. Cell apoptosis was determined by flow cytometry analysisusing annexin-V and propidium iodide staining. Cell supernatants were collected for the detection of cytokine secretion by enzyme-linked immunosorbent assay.Results: We confirmed the specific priming effect of EMR2 on the response of neutrophils to formyl-Met-Leu-Phe by measuring the production of reactiveoxygen species. Furthermore, we showed that EMR2 ligation suppressesLPS-induced neutrophil survival. In addition, we demonstrated that ligationof EMR2 changes the secretion profiles of multiple cytokines, includinginterleukin (IL)-6, IL-8, and monocyte chemotactic protein-1. Finally, higherlevels of EMR2 were detected on neutrophils of liver cirrhosis patients andwere correlated to a pro-apoptotic phenotype.Conclusion: Collectively, the present data indicate a functional role for EMR2 in themodulation of neutrophil activation during inflammation.