Evidence that FTY720 induces T cell apoptosis in vivo

被引:53
作者
Nagahara, Y
Enosawa, S
Ikekita, M
Suzuki, S
Shinomiya, T
机构
[1] Natl Childrens Med Res Ctr, Div Res Promot, Setagaya Ku, Tokyo 1548509, Japan
[2] Sci Univ Tokyo, Fac Sci & Technol, Dept Appl Biol Sci, Chiba 2788510, Japan
[3] Natl Childrens Med Res Ctr, Dept Expt Surg & Bioengn, Setagaya Ku, Tokyo 1548509, Japan
来源
IMMUNOPHARMACOLOGY | 2000年 / 48卷 / 01期
关键词
FTY720; immunosuppressant; apoptosis; T cell; aly/aly mouse;
D O I
10.1016/S0162-3109(00)00181-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immunosuppressant FTY720 induces a drastic decrease in blood lymphocytes, especially T cells; a decrease which is assumed to be the immunosuppressive mechanism of this drug. FTY720 causes cell death in vitro in lymphocytes and leukemia cells. However, the deletion mechanism of blood lymphocytes in vivo remains unclear. We investigated whether administration of FTY720 induced lymphocyte apoptosis in blood circulation. A marked decrease in the number of blood lymphocytes was observed within an hour after a single oral administration of FTY720 at doses of 5-10 mg/kg in rats and mice. Experiments using fluorescein isothiocyanate (FITC)-Annexin V and APO-BRDU(TM) methods revealed that FTY720 induced blood lymphocyte apoptosis in a dose-dependent manner. On the other hand, lymphocyte homing to Peyer's patches was proposed as the mechanism underlying the blood lymphocyte decrease at these doses. However, similar results were obtained when using aly/aly mice, which lack Peyer's patches and lymph nodes. Thus, we concluded that apoptosis of blood lymphocytes was induced immediately after administration of FTY720, and the cells could be immediately scavenged by phagocytes or the reticuloendothelial system in addition to Peyer's patches homing. We also concluded that T cells were highly sensitive to FTY720, which induced apoptosis in vivo. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:75 / 85
页数:11
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