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有机锡化合物的淋巴细胞毒性和免疫抑制作用。二正丁基二氯化锡和二正辛基二氯化锡对移植物抗宿主反应、母细胞转化和E花环形成的抑制作用。

Lymphocytotoxicity and immunosuppression by organotin compounds. Suppression of graft-versus-host reactivity, blast transformation, and E-rosette formation by di-n-butyltindichloride and di-n-octyltindichloride.

作者信息

Seinen W, Vos J G, Brands R, Hooykaas H

出版信息

Immunopharmacology. 1979 Jul;1(4):343-55. doi: 10.1016/0162-3109(79)90031-6.

DOI:10.1016/0162-3109(79)90031-6
PMID:45404
Abstract

Di-n-butyltindichloride (DBTC) and di-n-octyltindichloride (DOTC) represent a new group of organometallic compounds with antilymphocytic properties. In rats they induce lymphocyte depletion in thymus and thymus-dependent areas of spleen and peripheral lymph nodes without signs of myelotoxicity or a generalized toxicity. The number and viability of cells isolated from thymus and peripheral lymphoid organs was severely decreased, whereas the number and viability of bone marrow cells was not reduced. Immunosuppressive properties of DBTC and DOTC are indicated, in this study, by a severe decrease of the graft-versus-host response and the response to the T-cell mitogens phytohemagglutinin and concanavalin A. The T-cell selectivity of these compounds is discussed. In vitro DBTC and DTOC are extremely cytotoxic. Blast transformation of human as well as rat thymocytes was already inhibited at concentrations as low as 0.02 micrograms DBTC (or 0.1 micrograms DOTC) ml medium. Also the E-rosette formation was inhibited at very low drug levels. The similarity of effects upon rat and human lymphocytes suggests that DBTC and DOTC acts in the same manner in rat and man and offers the possibility of a therapeutic use of these compounds.

摘要

二正丁基二氯化锡(DBTC)和二正辛基二氯化锡(DOTC)代表了一类具有抗淋巴细胞特性的新型有机金属化合物。在大鼠中,它们可导致胸腺以及脾脏和外周淋巴结中胸腺依赖区的淋巴细胞耗竭,且无骨髓毒性或全身毒性迹象。从胸腺和外周淋巴器官分离出的细胞数量和活力严重下降,而骨髓细胞的数量和活力并未降低。在本研究中,DBTC和DOTC的免疫抑制特性表现为移植物抗宿主反应以及对T细胞有丝分裂原植物血凝素和刀豆球蛋白A的反应严重降低。讨论了这些化合物的T细胞选择性。在体外,DBTC和DOTC具有极强的细胞毒性。在培养基中,低至0.02微克DBTC(或0.1微克DOTC)/毫升的浓度就能抑制人及大鼠胸腺细胞的母细胞转化。在极低的药物水平下,E花环形成也受到抑制。对大鼠和人淋巴细胞作用的相似性表明,DBTC和DOTC在大鼠和人中的作用方式相同,为这些化合物的治疗应用提供了可能性。

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1
Lymphocytotoxicity and immunosuppression by organotin compounds. Suppression of graft-versus-host reactivity, blast transformation, and E-rosette formation by di-n-butyltindichloride and di-n-octyltindichloride.有机锡化合物的淋巴细胞毒性和免疫抑制作用。二正丁基二氯化锡和二正辛基二氯化锡对移植物抗宿主反应、母细胞转化和E花环形成的抑制作用。
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[The effect of di-n-octyl tin dichloride (DOTC) on immunocompetent organs and immunoreactivity of rats].
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引用本文的文献

1
Selective inhibition of immature CD4-CD8+ thymocyte proliferation, but not differentiation, by the thymus atrophy-inducing compound di-n-butyltin dichloride.胸腺萎缩诱导化合物二正丁基二氯化锡对未成熟CD4-CD8+胸腺细胞增殖具有选择性抑制作用,但对其分化无影响。
Immunology. 1994 Feb;81(2):261-7.
2
Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.化学诱导的胸腺萎缩恢复始于CD4-CD8-CD2高TcRαβ-/低胸腺细胞,并导致CD4-CD8-TcRαβ高胸腺细胞形成增加。
Immunology. 1993 Apr;78(4):616-22.
3
Immunotoxicology: suppressive and stimulatory effects of drugs and environmental chemicals on the immune system. A discussion.
免疫毒理学:药物和环境化学物质对免疫系统的抑制和刺激作用。讨论
Arch Toxicol. 1989;63(4):257-73. doi: 10.1007/BF00278639.
4
The organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+ thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta-/low CD2high thymoblast subset.有机锡诱导的胸腺萎缩,其特征为CD4+CD8+胸腺细胞耗竭,在此之前未成熟的CD4-CD8+TcRαβ-/低CD2高胸腺母细胞亚群会减少。
Immunology. 1992 Jun;76(2):203-8.