Inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression in fulminant hepatic failure.
OBJECTIVE
Inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) have important functions in inflammation and vasoregulation but their role in fulminant hepatic failure (FHF) is not well understood.


METHODS
Intrahepatic in situ staining and semi-quantification of iNOS and eNOS by immunohistochemistry in 25 patients with FHF, in 40 patients with chronic liver diseases (CLD) and in ten normal controls (NC).


RESULTS
Expression patterns of iNOS and eNOS differed. While in NC only faint iNOS expression was found in some Kupffer cells/macrophages and hepatocytes, eNOS was expressed constitutively in sinusoidal and vascular endothelial cells. In CLD, iNOS expression was induced in Kupffer cells/macrophages and hepatocytes, representing the main iNOS expressing cell types. Additionally, bile ducts, vascular endothelial cells and lymphocytes also expressed iNOS (P = 0.001). In contrast, no differences were found between eNOS expression in CLD and NC (P = 0.64). The same cell types expressed eNOS and iNOS in FHF but numbers of both were significantly enhanced, exceeding the levels seen in CLD (P < 0.001, P = 0.017).


CONCLUSIONS
Our data demonstrate that iNOS and eNOS are differently regulated in physiologic conditions and in liver disease. While eNOS seems to be involved in the physiological regulation of hepatic perfusion, strong upregulation of iNOS might contribute to inflammatory processes in FHF.
Leifeld
Ludger
L
Department of Internal Medicine I, University of Bonn, Sigmund Freud Strasse 25, D-53105 Bonn, Germany. l.leifeld@uni-bonn.de
Fielenbach
Magdalene
M
Dumoulin
Franz-Ludwig
FL
Speidel
Nicola
N
Sauerbruch
Tilman
T
Spengler
Ulrich
U
D001652:Bile Ducts / Q000201:enzymology; D002452:Cell Count; D004730:Endothelium, Vascular / Q000201:enzymology; D006801:Humans; D007728:Kupffer Cells / Q000201:enzymology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017093:Liver Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008214:Lymphocytes / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III