Induction of apoptosis of activated murine splenic T cells by cycloprodigiosin hydrochloride, a novel immunosuppressant.
Two types of immunosuppressants, cycloprodigiosin hydrochloride (cPrG) and L-leucyl-L-leucine methyl ester (LeuLeuOMe), both have the ability to selectively inhibit the lysosomal function, and a related compound to cPrG, prodigiosin 25-C, and LeuLeuOMe have been reported to selectively inhibit the T cell function in vitro. We therefore examined the cell-type specificity of cPrG and LeuLeuOMe using murine splenocytes. Concanavalin A (Con A)- and lentil lectin-induced proliferation was suppressed by cPrG more profoundly than lipopolysaccharide-induced proliferation. At the optimal concentration, Con A induced the proliferation of both CD4+ and CD8+ cells, whereas at a supra-optimal concentration Con A induced rather selective proliferation of CD8+ cells. Irrespective of the dose of Con A, CD4+ and CD8+ cells were equally affected by cPrG. In contrast, LeuLeuOMe induced the selective loss of CD8+ cells. cPrG enhanced the apoptosis of murine splenocytes and nylon fiber column-purified T cells cultured in the presence of Con A, as shown by the decrease in cell size and/or DNA fragmentation. Overall, this study revealed that the cell-type specificity of cPrG is different from that of LeuLeuOMe, and that the immunosuppression by cPrG is associated with apoptosis.
Azuma
T
T
Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
Watanabe
N
N
Yagisawa
H
H
Hirata
H
H
Iwamura
M
M
Kobayashi
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011758:Pyrroles / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D007166:Immunosuppressive Agents; D007211:Indoles; D008070:Lipopolysaccharides; D011758:Pyrroles; D003208:Concanavalin A; C108328:cycloprodigiosin