Description
- Abstract:
- About 7.1% of Americans older than 18 have been reported to abuse alcohol. Chronic alcoholics are more susceptible to infections. In this regard, higher incidences of lung infection caused by several bacteria and viruses have been reported in humans. Hepatitis C virus (HCV), a primary cause of acute and chronic liver diseases, is also a major problem in alcoholics. Additionally, murine models of chronic ethanol consumption have been shown to be more susceptible to bacterial and viral diseases. We have recently revealed in a chronic ethanol murine model that generation of HCV viral NS5 protein specific CD4+ and CD8+ T-cell responses were impaired and CD8+ T-cell activity could be restored by adoptive transfer of dendritic cells (DCs) derived from isocaloric pair-fed control but not from ethanol-fed animals. These findings suggested that impaired cellular immunity may be due, in part, to alcohol induced intrinsic defects in DCs. In chapter 1, attempts were made to explore the cellular mechanisms of these defects that impair exogenous antigen presentation by splenic DCs. We observed a reduction in the ability of DCs to present exogenous OVA protein to primary and DO11 T-cells. Processing of endocytosed antigens were unaltered, yet peptide-MHCII complex formation and presentation on the cell surface of DCs was reduced after chronic ethanol exposure in vivo. The reduced T-cell activation was not due, entirely, to reduced peptide-MHCII presentation. Furthermore, addition of several cytokines produced by ethanol-exposed DCs back to DC:T cell co-cultures or neutralization of IL-10 were unable to restore the impaired T-cell activation suggesting that the process was not reversible by this stage. In chapter 3, ethanol induced changes in gene expression profile of mature and immature DCs were explored. Finally, in chapter 4, two chronic ethanol rat models were employed to investigate the influence of alcoholic liver disease (ALD) on DC function. In the ALD-sensitive Long Evans rats, DCs displayed a less-mature phenotype in terms of costimulatory molecule expression, cytokine secretion and allogeneic antigen presentation compared to ALD-resistant Fisher strain. These results suggest that liver disease produced by chronic ethanol consumption has a major effect on DC function.
- Notes:
- Thesis (Ph.D. -- Brown University (2011)
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Citation
Eken, Ahmet,
"EFFECTS OF CHRONIC ETHANOL CONSUMPTION ON SPLENIC DENDRITIC CELL FUNCTIONS"
(2011).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z03J3B6G
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....