Linked Life Data

8781346

Source:http://linkedlifedata.com/resource/pubmed/id/8781346

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-12-4
pubmed:abstractText
Concanavalin A (Con A) induces T-cell-mediated hepatic injury in vivo, although Con A-stimulated lymphocytes are not cytotoxic to normal hepatocytes in vitro. This contradiction makes the mechanism of Con A-induced hepatitis elusive. In this study, we demonstrate that Con A but not tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), or actinomycin D (ActD) induced the susceptibility of hepatocytes to activated autologous lymphocyte cytotoxicity. Con A sensitized hepatocytes within 30 minutes after the stimulation in a dose-dependent fashion. The cytotoxicity was dose-dependently inhibited by either a Con A ligand, alpha-methyl mannoside, or a perforin inhibitor, concanamycin A (CMA), but not by anti-Fas ligand antiserum. In addition, Con A-treated hepatocytes were not sensitive to autologous activated lymphocytes from a perforin-deficient mouse, while hepatocytes from lpr mice were sensitized by Con A. In fact, Con A did not induce liver injury in perforin-deficient mice within the concentration employed in this study. Therefore, we conclude that the cytotoxicity was mediated through perforin/granzymes but not through the Fas/Fas ligand pathway. The cytotoxicity was inhibited by anti-intercellular adhesion molecule-1 (ICAM-1)/LFA-1 antibodies, but not by anti-VCAM-1/VLA-4 antibodies, both in vitro and in vivo. The cytotoxicity appears to be caused by CD8+ T cells; however, the cytokines from activated CD4+ T cells play a critical role in the pathogenesis of the hepatitis in vivo, because administration of anti-IFN-gamma antibodies inhibited the occurrence of the hepatitis. In conclusion, Con A-induced hepatitis is thought to be dominantly mediated by a perforin-dependent pathway through ICAM-1/LFA-1 interaction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
702-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Concanavalin A induces perforin-mediated but not Fas-mediated hepatic injury.
pubmed:affiliation
Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama, Japan.
pubmed:publicationType
Journal Article