Lombardi P, Fournier M, Bernier J, Mansour S, Neveu P, Krzystyniak K
Département des Sciences Biologiques, Université du Québec à Montréal, Canada.
Int J Immunopharmacol. 1991;13(8):1073-84. doi: 10.1016/0192-0561(91)90158-4.
The cytotoxicity, immunotoxicity and immunomodulatory potential of four dithiocarbamate derivatives were assessed and compared with the effects of Immuthiol (diethyl dithiocarbamate, DE-DTC) in mice. Cellular stimulation and cell viability were examined after in vitro exposure of spleen lymphocytes to selected DTC analogues: N-methyl-D-glucamine dithiocarbamate (NMG-DTC), dimethyl dithiocarbamate (DM-DTC), dibuthyl dithiocarbamate (DB-DTC) and diisobuthyl dithiocarbamate (DIB-DTC). Lymphocyte activation by plant and bacterial mitogens: concanavalin A (Con A), phytohaemagglutinin (PHA), lipopolysaccharide (LPS) and allogeneic stimulation of cells in mixed lymphocyte reaction (MLR) were examined in vitro in the presence of 10(-4)-10(-9) g/ml DE-DTC and other selected DTC derivatives. No direct in vitro lymphoproliferative activity of DTC derivatives was observed, although a relatively stronger cytotoxicity with DE-DTC and DM-DTC was noted. In addition, the in vivo effects of DTC derivatives were examined by cytofluorometric profile of splenic and bone marrow cells as well as in mitogenic and allogenic responses, after i.v. exposures of animals to two subsequent (25 mg/kg b.w.) doses of the chemical. Less cytotoxic DIB-DTC, NMG-DTC and DB-DTC expressed weak in vivo immunostimulatory potential when compared with the effect of DE-DTC, whereas the effects of DM-DTC on alloantigenic and mitogenic lymphocyte stimulation were comparable with the known effects of DE-DTC. Cytofluorometric studies showed that the number of cytotoxic/suppressor T-cells (Ts) and helper T-cells (Th) in the cell was increased by DE-DTC and NMG-DTC only. In addition, DM-DTC appeared to affect the Ts/Th ratio. DE-DTC did not affect the B-cell subpopulation, whereas other derivatives induced marked modifications of the pre-B-cell subpopulations in bone marrow. Our data suggest that in vivo the immunostimulatory effect of DM-DTC could be accompanied with major changes in bone marrow B-cell frequency and alteration of spleen Ts/Th ratio.
评估了四种二硫代氨基甲酸盐衍生物的细胞毒性、免疫毒性和免疫调节潜力，并与免疫硫醇（二乙基二硫代氨基甲酸盐，DE-DTC）对小鼠的作用进行了比较。在体外将脾淋巴细胞暴露于选定的二硫代氨基甲酸盐类似物：N-甲基-D-葡糖胺二硫代氨基甲酸盐（NMG-DTC）、二甲基二硫代氨基甲酸盐（DM-DTC）、二丁基二硫代氨基甲酸盐（DB-DTC）和二异丁基二硫代氨基甲酸盐（DIB-DTC）后，检测细胞刺激和细胞活力。在存在10(-4)-10(-9) g/ml DE-DTC和其他选定的二硫代氨基甲酸盐衍生物的情况下，体外检测植物和细菌有丝分裂原对淋巴细胞的激活作用：刀豆球蛋白A（Con A）、植物血凝素（PHA）、脂多糖（LPS）以及混合淋巴细胞反应（MLR）中细胞的同种异体刺激。未观察到二硫代氨基甲酸盐衍生物的直接体外淋巴细胞增殖活性，尽管注意到DE-DTC和DM-DTC具有相对较强的细胞毒性。此外，在动物静脉注射两次后续剂量（25 mg/kg体重）的化学物质后，通过脾细胞和骨髓细胞的细胞荧光分析以及有丝分裂和同种异体反应来检测二硫代氨基甲酸盐衍生物的体内作用。与DE-DTC的作用相比，细胞毒性较小的DIB-DTC、NMG-DTC和DB-DTC表现出较弱的体内免疫刺激潜力，而DM-DTC对同种异体抗原和有丝分裂原淋巴细胞刺激的作用与DE-DTC的已知作用相当。细胞荧光分析表明，仅DE-DTC和NMG-DTC增加了细胞中毒性/抑制性T细胞（Ts）和辅助性T细胞（Th）的数量。此外，DM-DTC似乎影响Ts/Th比值。DE-DTC不影响B细胞亚群，而其他衍生物诱导骨髓中前B细胞亚群发生明显改变。我们的数据表明，在体内，DM-DTC的免疫刺激作用可能伴随着骨髓B细胞频率的重大变化和脾Ts/Th比值的改变。
