Document Detail


Bacterial lipopolysaccharide decreases thrombomodulin expression in the sinusoidal endothelial cells of rats -- a possible mechanism of intrasinusoidal microthrombus formation and liver dysfunction.
MedLine Citation:
PMID:  12480554     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: To elucidate the mechanism of liver dysfunction occurring in patients with sepsis, we evaluated the effect of bacterial lipopolysaccharide (LPS) on the expression of thrombomodulin (TM) in rat sinusoidal endothelial cells (SECs) and the therapeutic efficacy of exogenous recombinant TM. METHODS: We induced endotoxemia in rats by bolus intraperitoneal injection of LPS. TM antigen levels within tissues were assessed by immunohistochemistry. We measured TM in cultured SECs by enzyme immunoassay, functional analysis and real-time polymerase chain reaction (PCR). RESULTS: TM antigen and activity levels were significantly decreased in SECs isolated from LPS-treated rats after 3 and 6 h treatment, and recovered after 12 h treatment, correlating with immunohistochemical observations. In contrast, TM messenger RNA was decreased after 6 and 12 h treatment, and slightly recovered after 24 h treatment. TM expression in cultured SECs isolated from normal rats was also reduced after treatment with LPS and tumor necrosis factor (TNF)-alpha in vitro. The increased levels of serum fibrin degradation products (FDP), fibrin deposition within liver sinusoids, injury of SECs and liver dysfunction induced by LPS in our rat model was improved by recombinant TM treatment. CONCLUSIONS: Decreased TM expression in SECs of LPS-treated rats may result in intrasinusoidal microthrombus formation and subsequent liver dysfunction during sepsis.
Authors:
Masane Kume; Tatsuya Hayashi; Hiroyuki Yuasa; Hitoshi Tanaka; Junji Nishioka; Masaru Ido; Esteban C Gabazza; Yoshifumi Kawarada; Koji Suzuki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hepatology     Volume:  38     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2002-12-13     Completed Date:  2003-08-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  9-17     Citation Subset:  IM    
Affiliation:
Department of Molecular Pathobiology, Mie University School of Medicine, Tsu-city, Mie 514-8507, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytokines / blood
Endothelium, Vascular / cytology,  metabolism*
Escherichia coli*
Immunohistochemistry
Lipopolysaccharides / pharmacology*
Liver Circulation*
Liver Diseases / etiology
RNA / metabolism
RNA, Messenger / metabolism
Rats
Recombinant Proteins / pharmacology
Thrombomodulin / antagonists & inhibitors*,  genetics,  metabolism
Thrombosis / etiology
Chemical
Reg. No./Substance:
0/Cytokines; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Thrombomodulin; 63231-63-0/RNA
Comments/Corrections
Comment In:
J Hepatol. 2003 Jan;38(1):2   [PMID:  12480552 ]

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