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Article: The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis

TitleThe Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis
Authors
Issue Date2003
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal Of Clinical Investigation, 2003, v. 112 n. 1, p. 58-66 How to Cite?
AbstractFibrin deposition and thrombosis within the microvasculature is now appreciated to play a pivotal role in the hepatocellular injury observed in experimental and human viral hepatitis. Importantly, the pathways by which fibrin generation is elicited in viral hepatitis may be mechanistically distinct from the classical pathways of coagulation induced by mechanical trauma or bacterial lipopolysaccharide (LPS). In the setting of murine hepatitis virus strain-3 (MHV-3) infection, a member of the Coronaviridae, activated endothelial cells and macrophages express distinct cell-surface procoagulants, including a novel prothrombinase, Fgl2/fibroleukin, which are important for both the initiation and localization of fibrin deposition. To assess the role of Fgl2/fibroleukin in murine viral hepatitis we generated a Fgl2/fibroleukin-deficient mouse. Peritoneal macrophages isolated from Fgl2/fibroleukin -/- mice did not generate a procoagulant response when infected with MHV-3. Fibrin deposition and liver necrosis were markedly reduced, and survival was increased in mice infected with MHV-3. To address the relevance of Fgl2/fibroleukin in human chronic viral hepatitis we studied patients with minimal and marked chronic hepatitis B. We detected robust expression of Fgl2/fibroleukin mRNA transcripts and protein in liver tissue isolated from patients with marked chronic hepatitis B. Fibrin deposition was strongly associated with Fgl2/fibroleukin expression. Collectively, these data indicate a critical role for Fgl2/fibroleukin in the pathophysiology of experimental and human viral hepatitis.
Persistent Identifierhttp://hdl.handle.net/10722/149620
ISSN
2015 Impact Factor: 12.575
2015 SCImago Journal Rankings: 8.764
References

 

DC FieldValueLanguage
dc.contributor.authorMarsden, PAen_US
dc.contributor.authorNing, Qen_US
dc.contributor.authorFung, LSen_US
dc.contributor.authorLuo, Xen_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorMendicino, Men_US
dc.contributor.authorGhanekar, Aen_US
dc.contributor.authorScott, JAen_US
dc.contributor.authorMiller, Ten_US
dc.contributor.authorChan, CWYen_US
dc.contributor.authorChan, MWCen_US
dc.contributor.authorHe, Wen_US
dc.contributor.authorGorczynski, RMen_US
dc.contributor.authorGrant, DRen_US
dc.contributor.authorClark, DAen_US
dc.contributor.authorPhillips, MJen_US
dc.contributor.authorLevy, GAen_US
dc.date.accessioned2012-06-26T05:56:10Z-
dc.date.available2012-06-26T05:56:10Z-
dc.date.issued2003en_US
dc.identifier.citationJournal Of Clinical Investigation, 2003, v. 112 n. 1, p. 58-66en_US
dc.identifier.issn0021-9738en_US
dc.identifier.urihttp://hdl.handle.net/10722/149620-
dc.description.abstractFibrin deposition and thrombosis within the microvasculature is now appreciated to play a pivotal role in the hepatocellular injury observed in experimental and human viral hepatitis. Importantly, the pathways by which fibrin generation is elicited in viral hepatitis may be mechanistically distinct from the classical pathways of coagulation induced by mechanical trauma or bacterial lipopolysaccharide (LPS). In the setting of murine hepatitis virus strain-3 (MHV-3) infection, a member of the Coronaviridae, activated endothelial cells and macrophages express distinct cell-surface procoagulants, including a novel prothrombinase, Fgl2/fibroleukin, which are important for both the initiation and localization of fibrin deposition. To assess the role of Fgl2/fibroleukin in murine viral hepatitis we generated a Fgl2/fibroleukin-deficient mouse. Peritoneal macrophages isolated from Fgl2/fibroleukin -/- mice did not generate a procoagulant response when infected with MHV-3. Fibrin deposition and liver necrosis were markedly reduced, and survival was increased in mice infected with MHV-3. To address the relevance of Fgl2/fibroleukin in human chronic viral hepatitis we studied patients with minimal and marked chronic hepatitis B. We detected robust expression of Fgl2/fibroleukin mRNA transcripts and protein in liver tissue isolated from patients with marked chronic hepatitis B. Fibrin deposition was strongly associated with Fgl2/fibroleukin expression. Collectively, these data indicate a critical role for Fgl2/fibroleukin in the pathophysiology of experimental and human viral hepatitis.en_US
dc.languageengen_US
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.orgen_US
dc.relation.ispartofJournal of Clinical Investigationen_US
dc.titleThe Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitisen_US
dc.typeArticleen_US
dc.identifier.emailChan, CWY:camchan@hku.hken_US
dc.identifier.authorityChan, CWY=rp01311en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1172/JCI200318114en_US
dc.identifier.scopuseid_2-s2.0-0042867244en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0042867244&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume112en_US
dc.identifier.issue1en_US
dc.identifier.spage58en_US
dc.identifier.epage66en_US
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMarsden, PA=7201783899en_US
dc.identifier.scopusauthoridNing, Q=7004228866en_US
dc.identifier.scopusauthoridFung, LS=7101721367en_US
dc.identifier.scopusauthoridLuo, X=7402871230en_US
dc.identifier.scopusauthoridChen, Y=7601429475en_US
dc.identifier.scopusauthoridMendicino, M=7003345072en_US
dc.identifier.scopusauthoridGhanekar, A=6603401476en_US
dc.identifier.scopusauthoridScott, JA=7407332640en_US
dc.identifier.scopusauthoridMiller, T=7403948723en_US
dc.identifier.scopusauthoridChan, CWY=12240386600en_US
dc.identifier.scopusauthoridChan, MWC=36941295800en_US
dc.identifier.scopusauthoridHe, W=55218921400en_US
dc.identifier.scopusauthoridGorczynski, RM=35431895200en_US
dc.identifier.scopusauthoridGrant, DR=35425624400en_US
dc.identifier.scopusauthoridClark, DA=36079434600en_US
dc.identifier.scopusauthoridPhillips, MJ=35425039700en_US
dc.identifier.scopusauthoridLevy, GA=35391580500en_US

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