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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-1-13
pubmed:abstractText
Murine Hepatitis Virus Strain 3 (MHV-3) produces fulminant hepatitis with 80-90% mortality in Balb/cJ mice. Previous studies in our laboratory have shown that peritoneal macrophages from MHV-3 infected mice produce a procoagulant (PCA) which has the ability to cleave prothrombin to thrombin (prothrombinase) encoded by the gene fgl2 located on chromosome 5. PCA accounts for sinusoidal thrombosis and hepatic necrosis and the necrosis and mortality can be prevented by treatment of animals with a monoclonal antibody to PCA. These present studies were designed to examine the expression of this gene (mRNA by Northern analysis and in situ hybridization) and the gene product PCA (immunochemistry) in tissues recovered from MHV-3 infected Balb/cJ mice in an attempt to explain the liver specific nature of MHV-3 disease. Fgl2 gene expression was detected as early as 8 hours after MHV-3 infection which persisted to 48 hours in the liver, spleen and lungs whereas no gene expression was seen in the brain or kidneys despite the fact that equivalent viral titers were detected in all tissues at all times. In the liver, fgl2 gene expression was confined to endothelial and Kupffer cells with no expression in hepatocytes. Immunochemistry localized the PCA protein to Kupffer cells and endothelial cells and necrotic foci within the liver. No PCA protein was detected by immunochemistry in any other tissues at any time during the course of MHV-3 infection. These results explain the liver specific nature (fulminant hepatitis) of MHV-3 infection and provides further evidence for the role of PCA in the pathogenesis of fulminant hepatitis. MHV-3 induces selective transcription of the gene fgl2 and only hepatic reticuloendothelial cells produce functional protein (PCA) which is known to account for fulminant hepatic failure produced by MHV-3.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2598
pubmed:author
pubmed:issnType
Print
pubmed:volume
440
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-18
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Expression of the fgl2 and its protein product (prothrombinase) in tissues during murine hepatitis virus strain-3 (MHV-3) infection.
pubmed:affiliation
Department of Multi Organ Transplantation Program and Medicine, Toronto Hospital, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't