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Clinical relevance and cellular source of elevated soluble urokinase plasminogen activator receptor (su PAR ) in acute liver failure
Author(s) -
Koch Alexander,
Zimmermann Henning W.,
Gassler Nikolaus,
Jochum Christoph,
Weiskirchen Ralf,
Bruensing Jan,
Buendgens Lukas,
Dückers Hanna,
Bruns Tony,
Gerken Guido,
Neumann Ulf P.,
Adams David H.,
Trautwein Christian,
Canbay Ali,
Tacke Frank
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12512
Subject(s) - liver failure , receptor , urokinase receptor , medicine , chemistry , cancer research
Background & Aims Acute liver failure ( ALF ) is a life‐threatening condition with a high mortality rate. The expression of urokinase plasminogen activator receptor (uPAR, CD87) and release of its shedded receptor into serum as soluble uPAR (suPAR) have been closely related to immune activation and prognosis in systemic inflammation and cirrhosis. We now aimed at investigating the clinical relevance and cellular source of uPAR and circulating suPAR in ALF. Methods Serum suPAR concentrations were measured in 48 ALF patients and 62 healthy controls from a German liver transplantation centre. Hepatic immune cell subsets and uPAR expression were studied by FACS, qPCR and immunohistochemistry. Results Circulating suPAR levels were significantly increased in ALF patients, independent from the underlying aetiology, in comparison to controls. Serum suPAR concentrations were closely correlated with parameters reflecting liver cell injury, decreased liver function and the model of end‐stage liver disease ( MELD ) score in ALF patients. By immunohistochemistry from explanted livers, ALF was associated with distinct immune cell accumulation and strong up‐regulation of intrahepatic uPAR mRNA expression. CD87 (uPAR) expression was specifically detected on intrahepatic ‘non‐classical’ monocytes (CD14 + CD16 + ), NKT and CD56 dim NK cells isolated from human liver, but not on parenchymal or other non‐parenchymal hepatic cell types. Membrane‐bound uPAR was rapidly cleaved from monocytes upon inflammatory stimulation by lipopolysaccharide (LPS) and partially by co‐cultured lymphocytes. Conclusions Similar to its prognostic properties in patients with sepsis or cirrhosis, intrahepatic uPAR activation and serum suPAR concentrations might serve as an interesting biomarker in ALF.