CELL TYPE-ORIENTED DIFFERENTIAL MODULATORY ACTIONS OF SAIKOSAPONIN-D ON GROWTH-RESPONSES AND DNA FRAGMENTATION OF LYMPHOCYTES TRIGGERED BY RECEPTOR-MEDIATED AND RECEPTOR-BYPASSED PATHWAYS

We examined the immunoregulatory action of saikosaponin-d (SSd), which was isolated from the root of Bupleurum talcatum L. and had a steroid-like structure, on murine thymocytes, and compared the action with that on spleen cells. Constitutive DNA synthesis or the growth response stimulated with anti-CD3mAb of thymocytes were down-regulated by 3 mu g/ml SSd, whereas with spleen cells these were up-regulated by the same concentration of SSd. On the other hand, 3 mu g/ml of SSd greatly up-regulated the growth response and interleukin 2 (IL-2)/interleukin 4 (IL-4) production induced through a receptor-bypassed pathway by calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA) in thymocytes, whereas it only slightly up-regulated them in spleen cells. Moreover, the same concentration of SSd inhibited DNA fragmentation in thymocytes induced by A23187 or PMA. These results suggest a unique cell type-dependent immuno-modulatory action of SSd.