Pestka J J, Dong W, Warner R L, Rasooly L, Bondy G S
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224.
Food Chem Toxicol. 1990 Oct;28(10):693-9. doi: 10.1016/0278-6915(90)90145-d.
Prolonged dietary exposure of mice to the trichothecene vomitoxin induces abnormally high levels of serum IgA and kidney mesangial IgA accumulation in a manner that is highly analogous to the human glomerulonephritis IgA nephropathy. In this study, the capacity of Peyer's patch and splenic lymphocytes to produce IgA and IgG were compared in B6C3F1 mice that were fed diets with and without 25 ppm vomitoxin for up to 12 wk. Serum IgA increased 2-, 4- and 8-fold after 4, 8 and 12 wk, respectively, of vomitoxin exposure and it became the primary serum isotype, whereas serum IgG was unaffected. On termination of the experiment there were increased numbers of IgA-secreting cells in Peyer's patches after 8 wk of toxin exposure and in the spleen after 4, 8 and 12 wk of toxin exposure. There were also increased numbers of IgG-secreting cells in Peyer's patches on termination of the experiment at 4, 8 and 12 wk but no effects was observed in the spleen. Supernatant IgA and IgA-secreting cell numbers were also markedly elevated in lymphocyte cultures obtained from Peyer's patches and, to a lesser extent, from spleens of treated mice compared with controls. Based on output of treated mice relative to corresponding controls, IgA secretion was greatest in concanavalin-A-stimulated and unstimulated Peyer's patch cultures. Enhanced IgG secretion and IgG-secreting cells were also observed in mitogen-stimulated and unstimulated Peyer's patch lymphocyte cultures of treated relative to control mice, but differences in splenocyte cultures were negligible. Based on total Ig output, IgA production was 8- to 20-fold greater than IgG production in both control and treatment Peyer's patch cultures. In contrast, vomitoxin treatment caused a shift from primarily IgG production in lipopolysaccharide-stimulated spleen cultures to equivalent IgA production. These data provide in vitro evidence that ingestion of vomitoxin promotes terminal differentiation of IgA-secreting progenitors in the Peyer's patch and, to a lesser extent, in the spleen. These functional changes are consistent with the shift from IgG to IgA as the primary serum isotype.
小鼠长期饮食接触单端孢霉烯族呕吐毒素会诱导血清IgA水平异常升高以及肾脏系膜IgA蓄积，其方式与人类肾小球肾炎IgA肾病高度相似。在本研究中，对喂食含25 ppm呕吐毒素和不含呕吐毒素饲料长达12周的B6C3F1小鼠的派尔集合淋巴结和脾脏淋巴细胞产生IgA和IgG的能力进行了比较。在接触呕吐毒素4周、8周和12周后，血清IgA分别增加了2倍、4倍和8倍，并成为主要的血清同种型，而血清IgG未受影响。实验结束时，毒素暴露8周后派尔集合淋巴结中分泌IgA的细胞数量增加，毒素暴露4周、8周和12周后脾脏中分泌IgA的细胞数量增加。在实验于4周、8周和12周结束时，派尔集合淋巴结中分泌IgG的细胞数量也增加，但在脾脏中未观察到影响。与对照组相比，从处理小鼠的派尔集合淋巴结获得的淋巴细胞培养物中上清液IgA和分泌IgA的细胞数量也显著升高，在较小程度上，从脾脏获得的培养物中也是如此。根据处理小鼠相对于相应对照组的产量，在伴刀豆球蛋白A刺激和未刺激的派尔集合淋巴结培养物中IgA分泌最多。与对照小鼠相比，在处理小鼠的有丝分裂原刺激和未刺激的派尔集合淋巴结淋巴细胞培养物中也观察到IgG分泌增强和分泌IgG的细胞增加，但脾细胞培养物中的差异可忽略不计。基于总Ig产量，在对照和处理的派尔集合淋巴结培养物中，IgA产生比IgG产生大8至20倍。相反，呕吐毒素处理导致脂多糖刺激的脾脏培养物中从主要产生IgG转变为产生等量的IgA。这些数据提供了体外证据，表明摄入呕吐毒素可促进派尔集合淋巴结中分泌IgA祖细胞的终末分化，在较小程度上也促进脾脏中分泌IgA祖细胞的终末分化。这些功能变化与作为主要血清同种型从IgG向IgA的转变一致。
