EFFECT OF TRICHOTHECENE MYCOTOXINS ON IGA PRODUCTION

倍半萜类真菌毒素是一类倍半萜类化合物， 真菌代谢物，其中包括一些最有效的蛋白质 已知的合成抑制剂。 由于古猿经常 在谷物中发现，在 经过碾磨和加工，它们进入了食物链。 这些 呕吐毒素在美国食品供应中最常见。 小鼠摄入呕吐毒素后， 血清伊加。 据推测， 青霉烯类真菌毒素损害伊加的正常调节 生产，这导致血清伊加的积累。 本提案的总体目标是了解细胞 基础，通过这些基础，多烯调节伊加的产生， 粘膜和全身隔室，并将这种作用与 潜在的健康危害与摄入这些 自然产生的霉菌毒素 使用小鼠模型，四（4） 提出了具体目标。 第一个目标是 测定体外暴露于呕吐毒素对 巨噬细胞和T细胞调节脾脏中伊加的产生， 派尔集合淋巴结（PP）培养物。 第二，在体内的影响 呕吐毒素暴露对调节伊加产生的影响将是 通过定量脾和PP中的体外伊加分泌来评估。 衍生淋巴细胞培养物，测量分泌IgA的B细胞和 脾脏和PP中调节性T细胞频率和监测 粘膜和全身伊加对口服抗原攻击的应答。 第三，体内呕吐毒素暴露后的伊加分布将 通过监测血清总伊加的变化来表征， 分泌伊加和血清单体：聚合型伊加的比率;以及 通过测定肾系膜中伊加沉积的可能性。 最后，噻吩结构将与 体外培养中的伊加产生。

The trichothecene mycotoxins are a group of sesquiterpenoid fungal metabolites, that include some of the most potent protein synthesis inhibitors known. Since trichothecenes are frequently found in cereal grains and are recalcitrant to inactivation during milling and processing, they enter the food chain. Of these vomitoxin is encountered most often in the U.S. food supply. Ingestion of vomitoxin by mice results in marked increases in serum IgA. It is hypothesized that dietary exposure to trichothecene mycotoxins impairs normal regulation of IgA production and that this results in accumulation of serum IgA. The overall goals of this proposal are to understand the cellular basis by which trichothecenes modulate IgA production within the mucosal and systemic compartments and relate this effect to potential health hazards associated with ingestion of these naturally-occurring mycotoxins. Using the mouse model, four (4) specific objectives are proposed. The first objective will be to determine the effects of in vitro exposure to vomitoxin on macrophage and T cell regulation of IgA production in spleen and Peyer's patch (PP) cultures. Second, the effects of in vivo vomitoxin exposure on regulation of IgA production will be assessed by quantitating in vitro IgA secretion in spleen and PP- derived lymphocyte cultures, measuring IgA-secreting B cell and T regulatory cell frequency in spleen and PP, and monitoring mucosal and systemic IgA response to oral antigen challenge. Third, IgA distribution following in vivo vomitoxin exposure will be characterized by monitoring changes in total serum IgA, secretory IgA, and ratio of serum monomeric:polymeric IgA; and by determining potential for IgA deposition in kidney mesangium. Finally trichothecene structure will be related to modulation of IgA production in in vitro cultures.