Effects of FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1, 3-propanediol HCl), a novel immunosuppressant, were examined on neurons and thymocytes respectively dissociated from rat brains and thymus glands using a flow cytometer to see if FTY720 exerts cytotoxic actions not only on spleen cells as previously reported but also on the other cells. FTY720 at a concentration of 10 μM deteriorated almost all of the thymocytes, while it was not the case for brain neurons. FTY720 increased the intracellular concentration of Ca
2+ ([Ca
2+]
i) of thymocytes in both the presence and absence of external Ca
2+, although the [Ca
2+]
i increased by FTY720 in the presence of external Ca
2+ was much greater than that in the absence of external Ca
2+. Thus, FTY720 may increase the membrane permeability of Ca
2+ and release Ca
2+ from intracellular Ca
2+ stores in thymocytes. Furthermore, the number of thymocytes stained with ethidium, a dye impermeant to intact membranes, time-dependently increased after drug application. Therefore, FTY720 at concentrations of 3 – 10 μM non-specifically increases the membrane permeability of thymocytes, resulting in necrotic cell death, although FTY720 at micromolar concentrations was reported to induce apoptosis of spleen cells.
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