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Ethanol Enhances Activation‐Induced Caspase‐3 Dependent Cell Death in T Lymphocytes
Author(s) -
Kelkar Sujata,
Dong Qing,
Xiao Yinghua,
JoshiBarve Swati,
McClain Craig J.,
Barve Shirish S.
Publication year - 2002
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2002.tb02547.x
Subject(s) - jurkat cells , apoptosis , programmed cell death , cd3 , t cell , stimulation , population , dna fragmentation , caspase 3 , microbiology and biotechnology , chemistry , biology , immunology , endocrinology , cd8 , biochemistry , medicine , immune system , environmental health
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 μg/ml) and Phytohemmaglutinin (1 μg/ml) or T‐cell receptor ligation (anti‐CD3 antibody (5 μg/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.