Pestka J J, Yan D, King L E
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824.
Food Chem Toxicol. 1994 Dec;32(12):1125-36. doi: 10.1016/0278-6915(94)90128-7.
The immunotoxic effects of the trichothecene vomitoxin (VT or deoxynivalenol) and other trichothecenes may be mediated by direct interaction with lymphocytes. In this study, flow cytometric cell cycle analysis was used in conjunction with phenotypic staining by specific fluorescein isothiocyanate antibody conjugates to assess the in vitro effects of VT and another protein synthesis inhibitor, cycloheximide (CHX), on apoptosis in specific T- and B-cell subsets within thymus, spleen and Peyer's patch (PP) cultures. Both VT and CHX markedly inhibited T-cell apoptosis in dexamethasone (9 alpha-fluoro-16 alpha-methylprednisolone)-induced (DEX+) cells isolated from thymus, spleen and PP. Apoptosis-associated internucleosomal DNA fragmentation in whole thymus cell lysates as measured by gel electrophoresis was qualitatively consistent with flow cytometry among the various treatment groups. VT and CHX induced apoptosis in untreated (DEX-) T, B. and IgA+ cells from spleen and PP, whereas the effects of VT and CHX on DEX-induced apoptosis in B and IgA+ cells from these sources were negligible. These findings indicate that VT could either inhibit or enhance programmed cell death in a concentration-dependent manner and that this was dependent on lymphocyte subset, tissue source and glucocorticoid induction.
单端孢霉烯族毒素呕吐毒素(VT或脱氧雪腐镰刀菌烯醇)及其他单端孢霉烯族毒素的免疫毒性作用可能是通过与淋巴细胞的直接相互作用介导的。在本研究中,流式细胞术细胞周期分析与特异性异硫氰酸荧光素抗体偶联物的表型染色相结合,以评估VT和另一种蛋白质合成抑制剂环己酰亚胺(CHX)对胸腺、脾脏和派尔集合淋巴结(PP)培养物中特定T细胞和B细胞亚群凋亡的体外影响。VT和CHX均显著抑制从胸腺、脾脏和PP分离的地塞米松(9α-氟-16α-甲基泼尼松龙)诱导的(DEX+)细胞中的T细胞凋亡。通过凝胶电泳测量的全胸腺细胞裂解物中与凋亡相关的核小体间DNA片段化在各治疗组中通过流式细胞术定性一致。VT和CHX诱导来自脾脏和PP的未处理(DEX-)T、B和IgA+细胞凋亡,而VT和CHX对这些来源的DEX诱导的B和IgA+细胞凋亡的影响可忽略不计。这些发现表明,VT可以以浓度依赖的方式抑制或增强程序性细胞死亡,并且这取决于淋巴细胞亚群、组织来源和糖皮质激素诱导。