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Induction of Apoptosis of Activated Murine Splenic T Cells by Cycloprodigiosin Hydrochloride, a Novel Immunosuppressant

T Azuma, N Watanabe, H Yagisawa, H Hirata, M Iwamura, Y Kobayashi

Immunopharmacology. 2000 Jan;46(1):29-37.

PMID: 10665777

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP56144173 Prodigiosin hydrochloride Prodigiosin hydrochloride 56144-17-3 Price
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