Imperial College London
Portrait Picture

DrWafaKhamri

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Teaching Fellow
 
 
 
//

Contact

 

w.khamri

 
 
//

Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Bernsmeier:2015:10.1053/j.gastro.2014.11.045,
author = {Bernsmeier, C and Pop, OT and Singanayagam, A and Triantafyllou, E and Patel, VC and Weston, CJ and Curbishley, S and Sadiq, F and Vergis, N and Khamri, W and Bernal, W and Auzinger, G and Heneghan, M and Ma, Y and Jassem, W and Heaton, ND and Adams, DH and Quaglia, A and Thursz, MR and Wendon, J and Antoniades, CG},
doi = {10.1053/j.gastro.2014.11.045},
journal = {Gastroenterology},
pages = {603--615.e14},
title = {Patients with acute-on-chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK},
url = {http://dx.doi.org/10.1053/j.gastro.2014.11.045},
volume = {148},
year = {2015}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background & AimsCharacteristics of decompensated cirrhosis and acute-on-chronic liver failure (ACLF) include susceptibility to infection, immuneparesis, and monocyte dysfunction. MER receptor tyrosine kinase (MERTK) is expressed by monocytes and macrophages and contributes to down-regulation of innate immune responses. We investigated whether MERTK expression is altered on monocytes from patients with liver failure.MethodsWe analyzed blood and liver samples collected from patients admitted to the liver intensive therapy unit at King’s College Hospital in London from December 2012 through July 2014. Patients had either ACLF (n = 41), acute decompensation of cirrhosis without ACLF (n = 9), cirrhosis without decompensation (n = 17), or acute liver failure (n = 23). We also analyzed samples from healthy individuals (controls, n = 29). We used flow cytometry to determine the level of innate immune function, and associated the findings with disease severity. We developed an assay to measure recruitment and migration of immune cells from the tissue parenchyma. Immunohistochemistry and confocal microscopy were used to determine levels of MERTK in bone marrow, liver, and lymph node tissues. We performed immunophenotype analyses and measured the production of tumor necrosis factor and interleukin 6 and intracellular killing of Escherichia coli by monocytes and peritoneal macrophages incubated with lipopolysaccharide, with or without an inhibitor of MERTK (UNC569).ResultsThe number of monocytes and macrophages that expressed MERTK was greatly increased in the circulation, livers, and lymph nodes of patients with ACLF, compared with patients with stable cirrhosis and controls. MERTK expression (mean fluorescence intensity) correlated with the severity of hepatic and extrahepatic disease and systemic inflammatory responses. Based on immunophenotype, migration, and functional analyses, MERTK-expressing monocytes migrate across the endothelia to localize into tissue sit
AU  - Bernsmeier,C
AU  - Pop,OT
AU  - Singanayagam,A
AU  - Triantafyllou,E
AU  - Patel,VC
AU  - Weston,CJ
AU  - Curbishley,S
AU  - Sadiq,F
AU  - Vergis,N
AU  - Khamri,W
AU  - Bernal,W
AU  - Auzinger,G
AU  - Heneghan,M
AU  - Ma,Y
AU  - Jassem,W
AU  - Heaton,ND
AU  - Adams,DH
AU  - Quaglia,A
AU  - Thursz,MR
AU  - Wendon,J
AU  - Antoniades,CG
DO  - 10.1053/j.gastro.2014.11.045
EP  - 615
PY  - 2015///
SN  - 0016-5085
SP  - 603
TI  - Patients with acute-on-chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK
T2  - Gastroenterology
UR  - http://dx.doi.org/10.1053/j.gastro.2014.11.045
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000349968200031&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.sciencedirect.com/science/article/pii/S0016508514014826?via%3Dihub
VL  - 148
ER  -
Download