Our previous studies show that lymphocytes express tyrosine hydroxylase (TH) and synthesize
catecholamines (CAs) including dopamine, epinephrine and norepinephrine, and that
the lymphocytes-derived endogenous CAs affect function of lymphocytes via autocrine/paracrine
pathways. Over recent years, induction of apoptosis has been suggested to be a possible
mechanism underlying the endogenous CAs-mediated lymphocyte proliferation, differentiation
and activation. However, direct effect of the lymphocytes-synthesized CAs on lymphocyte
apoptosis is less known. In the present study, TH inhibitor alpha-methyl-p-tyrosine
(alpha-MT) and monoamine oxydase inhibitor pargyline were employed to block the synthesis
and degradation of CAs in lymphocytes activated by concanavalin A (Con A). Apoptotic
cells and apoptosis-related genes and proteins, Bax, Bcl-2, Fas, Fas-Ligand (FasL)
and caspase-3, were examined in the lymphocytes treated with alpha-MT or pargyline
by means of Annexin V/propidium iodide (PI) staining, real-time PCR and Western blot
analyses, respectively. The treatment with alpha-MT of 10(-6) M and 10(-5) M (not
10(-7) M) notably reduced intracellular and supernatant DA, E and NE of the Con A-activated
lymphocytes in a dose-dependent manner, and correspondingly, the treatment induced
a remarkable decrease of apoptotic lymphocytes but not necrotic cells. The expression
of Bax, Fas, FasL and caspase-3 mRNAs and proteins was significantly inhibited in
the Con A-activated lymphocytes after the cells were treated with alpha-MT of 10(-6)
M and 10(-5) M; but the expression of Bcl-2 mRNA and protein was dramatically increased
by the alpha-MT treatment. Contrarily, the treatment with pargyline of 10(-6) M and
10(-5) M (not 10(-7) M) evidently increased the intracellular and supernatant DA,
E and NE contents of the Con A-activated lymphocytes in a dose-dependent manner, and
meanwhile, it caused a striking increase of apoptotic lymphocytes but not necrotic
cells. The expression of Bax, Fas, FasL and caspase-3 mRNAs and proteins in the Con
A-stimulated lymphocytes was remarkably enhanced by the treatment with pargyline of
10(-6) M and 10(-5) M, but the expression of Bcl-2 mRNA and protein was notably attenuated
by the pargyline treatment. These results imply that endogenous CAs synthesized and
secreted by lymphocytes accelerate lymphocyte apoptosis by altering fine balance between
the expression of antiapoptotic and proapoptotic markers at transcriptional and translational
levels, and suggest that both the death receptor pathway and the mitochondrial pathway
are involved in the endogenous CAs-induced apoptosis.