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新型免疫抑制剂FTY720的研究进展 被引量：5

Research Progress of Novel Immunosuppressant FTY720
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摘要 FTY720是一种来源于子囊菌冬虫夏草的新型免疫抑制剂,与常规免疫抑制剂环孢素、他克莫司、西罗莫司等相比具有不同的作用机制,其主要通过致淋巴细胞凋亡及归巢效应等起到免疫抑制的作用,在多种动物模型的同种异体移植中具有抑制移植物排斥作用,在人体肾脏移植中也呈较强的免疫抑制活性,故在临床器官移植及自身免疫性疾病的治疗等方面具有广泛的应用前景。 FTY720 is a biosynthetic compound derived from the metabolites of Isaria sinclairii. Its unique action mechanism appears to be distinctive from other known immunosuppressive agents, such as cyclosporin A, tacrolimus and sirolimus. FTY720 can function as an immunosuppressive agent through selective induction of apoptosis of lymphocytes and effect of lymphocytes homing, which are considered to be its potency of inhibiting graft rejection in various animal allotransplantation models and effecting in human＇s renal transplantation. It was approved or being developed for wide uses in organ transplantation and self-immunity diseases.
作者 高明明 高向东 顾觉奋
机构地区 中国药科大学生命科学与技术学院
出处 《国外医药（抗生素分册）》 CAS 2007年第5期215-218,224,共5页 World Notes on Antibiotics
关键词 免疫抑制剂 FTY720 器官移植 移植物排斥 自身免疫性疾病 作用机制 immunosuppressant FTY720 organ transplantation graft rejection self-immunity diseases mechanism of action
分类号 R593 [医药卫生—内科学]
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参考文献22

  • 1Kunzendorff U, Zieglar E, Kabelitz, et al. FTY720-the first compound of a new promising class of immunosuppressive drugs [J]. Nephrol Dial Transplant, 2004, 19(7): 1677
  • 2Welsch C A, Hagiwara S, Goetschy J F, et al. Ubiquitin pathway proteins influence the mechanism of action of the novel immunosuppressive drug FTY720 in Saccharomyces cercvisiae [J]. J Biol Chem, 2003, 278(29): 26976
  • 3Yopp A C, Fu S, Honig S M, et al. FTY720-enhanced T cell homing is dependent on ccr2, ccr5, ccr7, and cxcr4: evidence for distinct chemokine compartments [J]. J Immunol, 2004, 173:855
  • 4Mandala S, Hajdu R, Bergstrom J, et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists[J]. Science, 2002, 296 (5566):346
  • 5Seitz G, Boehmler A, Kanz L, et al. The role of sphingosine 1-phosphate receptors in the trafficking of hematopoietic progenitor cells [J]. Ann N Y Acad Sci, 2005, 1044:84
  • 6Lo C G, Xu Ying, Proia R L, et al. Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit[J]. JEM, 2005, 201 (2): 291
  • 7左利群,张雷.FTY720对小鼠外周血淋巴细胞的影响[J].中华器官移植杂志,2003,24(5):305-306. 被引量：1
  • 8Nagahara Y, Ikekita M, Shinomiya T, et al. Immunosuppressant FTY720 induces apoptosis by direct induction of permeability transition and release of cytochrome C from mitochondria [J]. J Immunol, 2000, 165(9): 3250
  • 9Allende M L, Sasaki T, Kawa H, et al. Mice deficient in sphingosine kinase .1 are rendered lymphopenic by FTY720 [J]. J Biol Chem, 2004, 279(50): 52487
  • 10Sanchez T, Estrada H T, Paik J H, et al. Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability [J]. J Biol Chem, 2003, 278(47): 47281

二级参考文献38

  • 1王根生.一氧化氮和肿瘤坏死因子在小鼠免疫性肝损伤中的作用及抗肝炎新药SY－801和SY－640的影响[J].生理科学进展,1996,27(1):47-49. 被引量：26
  • 2[1]Haruhito A, Shiro T, Naotsugu I, et al. Marked prevention of tumor growth and metastasis by a novel immunosuppressive Agent, FTY720, in Mouse Breast [J]. Cancer Research,2002, 62(5): 1 410- 1 419.
  • 3[2]Masayuki F, Xiao KL, Yusuke K, et al. Distinct pathways of apoptosis triggered by FTY720, etoposide, and anti-Fas antibody in human T-Lymphoma cell line (Jurkat Cells) [J].J Pharmacol Exp Ther, 2002, 300(3): 939-945.
  • 4[5]Klemens B, Robert L, Schmouder A, et al. First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients [J]. J Am Soc Nephrol, 2002, 13 (4):1 073- 1 083.
  • 5[6]Kovarik JM, Schmouder R, Barilla D, et al. Multiple-dose FTY720: tolerability, pharmacokinetics, and lymphocyte responses in healthy subjects [J]. J Clin Pharmacol, 2004,44(5): 532- 537.
  • 6[7]Brinkmann V , Davis MD , Heise CE , et al . The immune modulator FTY720 targets sphingosine 1-phosphate receptors[J]. J Biol Chem, 2002, 277(24): 21 453 - 21 457.
  • 7[8]Tanaka T, Takahara S, Hatori M, et al . A novel immuno suppressive drug, FTY720, prevents the cancer progression induced by cyclosporine [J]. Cancer Lett, 2002,181 (2):165- 171.
  • 8[9]Graler MH , Goetzl EJ . The immunosuppressant FTY720down-regulates sphingosine 1-phosphate G protein-coupled receptors [J]. FASEB J, 2004, 18(3): 551-553.
  • 9[10]Matloubian M , Lo CG , Cinamon G , et al . Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1 [J]. Nature, 2004,427(6 972):355 - 360.
  • 10[11]Andreas B, Frederic B, Piroska D, et al. Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases [J]. J Biol Chem, 2003, 278(48): 47 408 - 47 415.

共引文献30

同被引文献100

引证文献5

二级引证文献38

国外医药（抗生素分册）
2007年 第5期

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