Increased EMR2 expression on neutrophils correlates with disease severity and predicts overall mortality in cirrhotic patients

Abstract

Patients with liver cirrhosis are susceptible to infections with high short-term mortalities. One CD97-related EGF-TM7 molecule, EMR2 (EGF-like molecule containing mucin-like hormone receptor 2), had been shown to regulate human neutrophil function, potentiate systemic inflammation. Nevertheless, EMR2 could also suppress neutrophil survival. Studying the role of EMR2 on neutrophil would be intriguing. 48 healthy volunteers and 100 cirrhotic patients were enrolled. Neutrophils were isolated from peripheral blood and cell surface markers were measured by flow cytometry.EMR2 expression levels correlated with CTP scores and increased further in patients with infections. These EMR2-expressed neutrophils were with activated phenotype, but with deranged functions like increased resting oxidative burst and impaired phagocytosis ability. Ligation of EMR2 could increase the phagoburst capacity but not the phagocytosis ability. Furthermore, neutrophils with higher EMR2 expression were more apoptotic and lost the LPS-induced neutrophil survival. Finally, EMR2 expressions on neutrophils correlated with infections and their levels greater than 25 had an AUC = 0.708 for predicting mortality. In conclusion, EMR2 expression levels correlated with CTP scores and increased further in cirrhotic patients with infections. These high EMR2-expressed neutrophils had activated phenotype but with deranged functions. Higher levels of these EMR2-expressed neutrophils correlated with infectious complications and predict mortality.

The Adhesion G Protein-Coupled Receptor GPR97/ADGRG3 Is Expressed in Human Granulocytes and Triggers Antimicrobial Effector Functions

“…As expected, EMR1, the human homolog of F4/80, was restricted to eosinophils (10, 37). Further confirming previous findings, EMR2, EMR3, and CD97 were found in all granulocytic lineages, although surface expression in neutrophilic granulocytes was absent/low in resting cells that upregulate surface expression during cellular activation (11, 12, 15, 38). GPR97 was detected at comparable levels in neutrophilic, eosinophilic, and basophilic granulocytes.…”

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

“…Granulocyte colony stimulating factor (G-CSF) treatment increased transendothelial migration of neutrophils from cirrhotic patients in vitro , suggesting this factor may be able to increase neutrophil recruitment to infected sites (50). Elevated expression of other neutrophil adhesion molecules, including LSEL [CD62L (50)] and ITGAM (CD11B) (37), which may contribute to alterations in neutrophil recruitment in vivo , have also been reported.…”

Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies

“…FHR1 activates the NLRP3 inflammasome in monocytes via the PLC and Ca 2+ activation pathways. RNAseq data derived from FHR1-induced monocytes suggested involvement of GPCR EMR2/ADGRE2, which induces inflammatory responses in macrophages 26, 39 . Specific inhibition of EMR2 confirmed FHR1 action via this receptor on monocytes.…”