Ethanol enhances activation-induced caspase-3 dependent cell death in T lymphocytes.
BACKGROUND
Clinical and experimental studies have shown that an important deleterious consequence of excessive alcohol consumption is immunosuppression, specifically, a depletion in the mature CD4+ T-cell population. A predominant mechanism involved in T-cell depletion is activation-induced cell death (AICD). Although it is well documented that ethanol intake can cause depletion of CD4+ T cells, the mechanism of how alcohol mediates its effects is unclear.


METHODS
The results were based on data from three separate experiments presented as mean +/- standard deviation (SD). Jurkat CD4+ T cells and peripheral blood lymphocytes were treated with 25 mM of ethanol (12-18 hr), followed by stimulation with mitogens Conconavalin A (5 microg/ml) and Phytohemmaglutinin (1 microg/ml) or T-cell receptor ligation (anti-CD3 antibody (5 microg/ml)) for 6 hr, and then harvested for measurement. The apoptotic cell death markers measured include cell viability, Caspase-3-like activity, and DNA fragmentation.


RESULTS
We demonstrate that alcohol pretreatment enhances AICD of Jurkat CD4+ T cells and peripheral blood lymphocytes upon activation by CD3-crosslinking or stimulation with Conconavalin A and Phytohemmaglutinin. Furthermore, we find that the ethanol-mediated enhancement of T cells to apoptosis involves increased activation of Caspase-3 and can be abrogated by treatment with a specific inhibitor of Caspase-3.


CONCLUSIONS
Our data indicate that ethanol can sensitize CD4+ T cells to enhanced stimulation-induced Caspase-3 activation and to subsequent AICD. This is, perhaps, an important mechanism in alcohol-induced immunosuppression.
Kelkar
Sujata
S
Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington, KY 40202, USA.
Dong
Qing
Q
Xiao
Yinghua
Y
Joshi-Barve
Swati
S
McClain
Craig J
CJ
Barve
Shirish S
SS
D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis* / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology
D002492:Central Nervous System Depressants; D007166:Immunosuppressive Agents; D000431:Ethanol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases