EFFECTS OF SEX HORMONE AND ENVIRONMENTAL ENDOCRINE DISRUPTORS ON GUT-ASSOCIATED LYMPHOID TISSUES

用分子生物学、显微镜和流式细胞术研究了环境内分泌干扰物对去势雌性小鼠免疫器官(Peyer S斑块)的影响.结果表明：(A)用雌激素受体α(ER)的单抗，环境内分泌干扰物处理的Peyer‘s斑块的ER水平分别是油处理对照组的1.2~2.5倍.(B)电子显微镜观察表明，EDC处理可引起淋巴细胞的凋亡，这些淋巴细胞被基质细胞(即巨噬细胞)包裹；(3)流式细胞仪分析显示，EDC可引起淋巴细胞亚群的改变：Peyer S斑块中抑制/细胞毒(CD_4-CD_8~+)细胞增多，辅助/诱导(CD_4+CD_8~-)细胞减少，由此推测EDC可能引起与T细胞功能密切相关的免疫器官的形态改变。此外，这些变化似乎主要源于EDC诱导的组织特异性基因表达。本研究的结果表明，我们必须认识到低剂量的EDC可以影响免疫干扰物能力的各种免疫反应的可能性。

The effect of environmental endocrine disruptors (EDC)on the immune organ (Peyer s patch) from castrated female mice was examined by molecular biologic, microscopic and flow cytometric techniques.Our findings were as follows : (a) using a monoclonal antibody to estrogen receptor-alpha (ER), ER level in the EDC-treated Peyer's patch was almost 1.2〜2.5 times that in oil-treated controls, respectively ; (b) an electron microscopic observation indicated EDC treatment to bring about apoptosis of lymphocytes which were embraced by stromal cells (i.e. macrophages) ; (c) flow cytometric analysis demonstrated EDC to induce the change of lymphocyte subsets : an increase in the suppressor/cytotoxic (CD4-CD8+) cells with decrease in the helper/inducer (CD4+CD8-) cells in Peyer s patch.It follows from the above findings that EDC may cause morphologic changes in the murine immune organs closely related to T cell function. In addition, these changes appear to derive mainly from EDC-induced tissuespeciic gene expression. The results of the present study suggest that we must recognize the possibility that a lowdose EDC can affect the various immune responses in the capacity of immune disruptors.