Metabolic and Chemical Origins of Cross-Reactive Immunological Reactions to Arylamine Benzenesulfonamides: T-Cell Responses to Hydroxylamine and Nitroso Derivatives
作者:J. Luis Castrejon、Sidonie N. Lavergne、Ayman El-Sheikh、John Farrell、James L. Maggs、Sunil Sabbani、Paul M. O’Neill、B. Kevin Park、Dean J. Naisbitt
DOI:10.1021/tx900329b
日期:2010.1.18
intermediates. For immune activation, female Balb-c strain mice were administered nitroso sulfonamides four times weekly for 2 weeks. After 14 days, isolated splenocytes were incubated with the parent compounds, hydroxylamine metabolites, and nitroso derivatives to measure antigen-specific proliferation. To explore the requirement of irreversible protein binding for spleen cell activation, splenocytes were
暴露于磺胺甲恶唑(SMX)与人类患者的T细胞介导的超敏反应有关。假定的代谢物亚硝基SMX可以刺激T细胞,该代谢物与蛋白质不可逆地结合。合成了三种芳胺苯磺酰胺,磺胺噻唑,磺胺嘧啶和磺胺吡啶的羟胺和亚硝基衍生物,并探讨了它们在小鼠中的T细胞刺激能力。亚硝基衍生物是通过三步法合成的,包括形成硝基和羟胺磺酰胺中间体。为了免疫激活,雌性Balb-c品系小鼠每周四次给药亚硝基磺酰胺,持续2周。14天后,将分离的脾细胞与母体化合物羟胺代谢物一起温育,和亚硝基衍生物来测量抗原特异性增殖。为了探索不可逆蛋白结合对脾细胞活化的需求,在存在或不存在谷胱甘肽的情况下,将脾细胞与亚硝基衍生物一起孵育。亚硝基磺酰胺致敏小鼠的脾细胞在用亚硝基衍生物而不是母体化合物刺激后增殖并分泌白介素(IL)-2,IL-4,IL-5和粒细胞单核细胞集落刺激因子。还用结构相关的磺酰胺的羟胺和亚硝基衍生物刺激了致敏小鼠的脾细胞增殖。谷胱甘