The Role of CD44 in Concanavalin A-Induced Hepatitis

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dc.contributor.authorChen, Daweien
dc.contributor.committeechairNagarkatti, Mitzien
dc.contributor.committeememberNagarkatti, Prakash S.en
dc.contributor.committeememberHoward, Rick Daleen
dc.contributor.departmentVeterinary Medical Sciencesen
dc.date.accessioned2011-08-06T16:06:20Zen
dc.date.adate2000-05-08en
dc.date.available2011-08-06T16:06:20Zen
dc.date.issued1999-02-18en
dc.date.rdate2001-05-08en
dc.date.sdate2000-05-08en
dc.description.abstractAdministration of Concanavalin-A (Con A) induces severe injury to the hepatocytes in mice and is considered to be a model for human hepatitis. In the current study, we investigated the role of CD44 in Con A induced hepatitis. Although immune cells have been identified as the causative agent of Con A-induced hepatitis, the exact mechanism of pathogenesis remains unclear. When Con A was injected into CD44 wild type (WT) mice, it induced hepatitis as evident from increased plasma aspartate aminotransferase (AST) levels accompanied by active infiltration of mononuclear cells in the liver and significant induction of apoptosis. Interestingly, Con A injected C57BL/6 CD44-knockout (KO) mice exhibited increased hepatitis with higher levels of apoptosis in the liver and increased plasma AST levels when compared to the CD44 WT mice. Also, transfer of T cells from Con A injected CD44-KO mice into CD44 WT mice induced higher levels of hepatitis when compared to transfer of similar cells from CD44 WT mice into CD44 WT mice. The increased hepatitis seen in CD44-KO mice was partially due to increased production of cytokines such as TNF-a, IL-2 and IFN-g, but not Fas or FasL. Also, it was not caused by altered presence of T cell subsets. The increased susceptibility of CD44 KO mice to hepatitis correlated with increased resistance of T cells from CD44 KO mice to undergo apoptosis when compared to the CD44 WT mice. Together, these data demonstrate that activated T cells use CD44 to undergo apoptosis, and dysregulation in this pathway could lead to increased pathogenesis in a number of diseases, including hepatitis.en
dc.description.degreeMaster of Scienceen
dc.format.mediumETDen
dc.identifier.otheretd-05082000-10420024en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05082000-10420024en
dc.identifier.urihttp://hdl.handle.net/10919/10102en
dc.publisherVirginia Techen
dc.relation.haspartChenThesis.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectApoptosisen
dc.subjectHepatitisen
dc.subjectCD44en
dc.subjectConcanavalin Aen
dc.titleThe Role of CD44 in Concanavalin A-Induced Hepatitisen
dc.typeThesisen
thesis.degree.disciplineVeterinary Medical Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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