Kerkvliet N I, Baecher-Steppan L, Claycomb A T, Craig A M, Sheggeby G G
Fundam Appl Toxicol. 1982 Mar-Apr;2(2):90-9. doi: 10.1016/s0272-0590(82)80121-8.
The effects of chronic dietary exposure to technical pentachlorophenol (PCP-T) on humoral immune responses in mice were examined. Primary and secondary splenic antibody responses to the T-dependent antigen, sheep red blood cells (SRBC), were examined in Swiss-Webster mice using our recently developed screening technique, the Hemolytic Antibody Isotope Release (HAIR) assay. To assess direct effects of PCP-T on B cells, the splenic plaque-forming cell response and serum antibody titers to the T-independent antigen, dinitrophenyl (DNP)-Ficoll, were examined. PCP-T exposure altered both the kinetics and the magnitude of the humoral antibody responses to SRBC and DNP-Ficoll. Peak splenic antibody production and serum antibody titers were delayed and the magnitude of the antibody responses were dose-dependently suppressed by PCP-T exposure. IgM responses appeared to be more sensitive to PCP-T-induced suppression than the IgG response. Significant depression of the IgM anti-SRBC splenic HAIR response was apparent as early as 2 weeks after initiation of PCP-T exposure and persisted for at least 8 weeks after termination of PCP-T feeding. Liver weight and serum lactate dehydrogenase (LD-L) and alanine aminotransferase (ALT) levels were significantly elevated during PCP-T exposure and returned to control levels after a 4-6 week recovery period. The immunotoxic effect of PCP on humoral immunity was observed only in animals exposed to technical grade PCP known to be contaminated with significant levels of other chlorinated phenols as well as non-phenolic impurities including chlorinated dioxins, furans, and diphenyl ethers. Animals exposed to analytical grade PCP did not exhibit depressed humoral immunity.
研究了长期饮食接触工业五氯苯酚(PCP-T)对小鼠体液免疫反应的影响。使用我们最近开发的筛选技术——溶血抗体同位素释放(HAIR)测定法,检测了瑞士韦伯斯特小鼠对T细胞依赖性抗原绵羊红细胞(SRBC)的初次和二次脾抗体反应。为了评估PCP-T对B细胞的直接影响,检测了对T细胞非依赖性抗原二硝基苯基(DNP)-Ficoll的脾空斑形成细胞反应和血清抗体滴度。PCP-T暴露改变了对SRBC和DNP-Ficoll的体液抗体反应的动力学和幅度。脾抗体产生峰值和血清抗体滴度延迟,抗体反应幅度受到PCP-T暴露的剂量依赖性抑制。IgM反应似乎比IgG反应对PCP-T诱导的抑制更敏感。早在PCP-T暴露开始后2周,IgM抗SRBC脾HAIR反应就出现了显著抑制,并在PCP-T喂养终止后至少持续8周。在PCP-T暴露期间,肝脏重量、血清乳酸脱氢酶(LD-L)和丙氨酸转氨酶(ALT)水平显著升高,并在4-6周的恢复期后恢复到对照水平。仅在暴露于已知被大量其他氯酚以及包括氯代二恶英、呋喃和二苯醚在内的非酚类杂质污染的工业级PCP的动物中观察到PCP对体液免疫的免疫毒性作用。暴露于分析级PCP的动物未表现出体液免疫抑制。