EMR2 receptor ligation modulates cytokine secretion profiles and cell survival of lipopolysaccharide-treated neutrophils.
BACKGROUND
Epidermal growth factor (EGF)-like module-containing mucin-like hormone receptor-like 2 (EMR2) is an adhesion G protein-coupled receptor previously shown 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 the cytokine expression profile and cell survival of lipopolysaccharide (LPS)-treated neutrophils.


METHODS
Neutrophils were treated with LPS in the absence or presence of the anti-EMR2 mAb, 2A1. Cell apoptosis was determined by flow cytometry analysis using 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 reactive oxygen species. Furthermore, we showed that EMR2 ligation suppresses LPS-induced neutrophil survival. In addition, we demonstrated that ligation of EMR2 changes the secretion profiles of multiple cytokines, including interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1. Finally, higher levels of EMR2 were detected on neutrophils of liver cirrhosis patients and were correlated to a pro-apoptotic phenotype.


CONCLUSIONS
Collectively, the present data indicate a functional role for EMR2 in the modulation of neutrophil activation during inflammation.
Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Tzu-Ying
TY
Chen
Tsong-Long
TL
Hwang
Chun-Yen
CY
Lin
Tsung-Nan
TN
Lin
Hsin-Yi
HY
Lai
Wen-Pin
WP
Tsai
Hsi-Hsien
HH
Lin
D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008103:Liver Cirrhosis / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
C412456:ADGRE2 protein, human; D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D009240:N-Formylmethionine Leucyl-Phenylalanine