HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/G75    most recent 00245.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Nedredal, G. I. Articles by Revhaug, A. Search for Related Content PubMed PubMed Citation Articles by Nedredal, G. I. Articles by Revhaug, A.

LIVER AND BILIARY TRACT

Significant contribution of liver nonparenchymal cells to metabolism of ammonia and lactate and cocultivation augments the functions of a bioartificial liver

¹Department of Digestive Surgery, University Hospital of Northern Norway, Tromsø; ²Surgical Research Laboratory, Institute of Clinical Medicine, and ³Department of Experimental Pathology, University of Tromsø, Tromsø; ⁴Department of Anesthesia and Intensive Care, University Hospital of Northern Norway, Tromsø; ⁵Department of Pharmacology, University of Tromsø, Tromsø; and ⁶Department of Obstetrics and Gynecology and ⁷Department of Clinical Chemistry, University Hospital of Northern Norway, Tromsø, Norway

Submitted 5 June 2006 ; accepted in final form 13 March 2007

A bioartificial liver (BAL) will bridge patients with acute liver failure (ALF) to either spontaneous regeneration or liver transplantation. The nitrogen metabolism is important in ALF, and the metabolism of nonparenchymal liver cells (NPCs) is poorly understood. The scope of this study was to investigate whether cocultivation of hepatocytes with NPCs would augment the functions of a BAL (HN-BAL) compared with a BAL equipped with only hepatocytes (H-BAL). In addition, NPCs were similarly cultivated alone. The cells were cultivated for 8 days in simulated microgravity with serum-free growth medium. With NPCs, initial ammonia and lactate production were fivefold and over twofold higher compared with later time periods despite sufficient oxygen supply. Initial lactate production and glutamine consumption were threefold higher in HN-BAL than in H-BAL. With NPCs, initial glutamine consumption was two- to threefold higher compared with later time periods, whereas initial ornithine production and arginine consumption were over four- and eightfold higher compared with later time periods. In NPCs, the conversion of glutamine to glutamate and ammonia can be explained by the presence of glutaminase, as revealed by PCR analysis. Drug metabolism and clearance of aggregated gamma globulin, probes administered to test functions of hepatocytes and NPCs, respectively, were higher in HN-BAL than in H-BAL. In conclusion, NPCs produce ammonia by hydrolysis of amino acids and may contribute to the pathogenesis of ALF. High amounts of lactate are produced by NPCs under nonhypoxic conditions. Cocultivation augments differentiated functions such as drug metabolism and clearance of aggregated -globulin.

liver sinusoidal endothelial cells; kidney-type glutaminase; acute liver failure; hyperammonemia; glutamine