ORGANOPHOSPHATE IMMUNOACTIVITY

这项研究试图确定免疫细胞功能的变化是由于 暴露在有机磷化合物中。这些化合物，作为一个类别，是 广泛用于农业(农药、杀菌剂)、工业 (增塑剂、添加剂、恢复剂)，以及日常 应用(草坪和花园产品、润滑剂、清漆)。上一首 研究已经清楚地证明了这些化合物的神经毒性作用。 化合物；根据这些数据确定了安全暴露水平。 然而，最近的信息表明，对免疫细胞的影响 系统的发生水平将显著低于 神经毒性。目前的研究重点是三苯基的影响。 磷酸盐--单核/巨噬细胞上的有机磷酸盐模型 血统。这些细胞是诱导和调节血管紧张素转换酶 免疫反应性；它们在免疫中也发挥着关键的效应作用。 这些反应在正常的发育和修复过程中很重要。 来自体内和体外研究的证据表明 单核/巨噬细胞系对有机磷敏感 化合物。 建议的研究，使用对照和处理的小鼠和人的原代 细胞培养和细胞系，研究三个特定领域 初步研究表明，TPP和TPP可以改变巨噬细胞的功能 相似的化合物。这些问题包括：(1)关键参数的更改 到抗原呈递和细胞间的合作。表面抗原 表达将通过荧光激活的细胞分选来确定 (FACS)、光镜和电子显微镜免疫细胞化学、酶联免疫吸附试验。 相关的IL-1、吞噬和抗原提呈试验将是 已执行。(2)TPP对成熟细胞酯酶活性的影响 以及处于分化途径不同阶段的细胞。光和 荧光显微镜和流式细胞仪分析酯酶活性将 搞定了。酯酶活性、表面抗原相关FACS分析 表达式，将执行单元格大小和复杂性。最近 开发了同时观察表面抗原和 将使用酯酶活性，以及对TPP的影响的研究 关于提取的酯酶同工酶。(3)前体细胞的改变 TPP暴露引起的分化和基因表达。前体细胞 罚金，可诱导分化为成熟 单核/巨噬细胞样细胞，将检查 分化特异性标记(例如，形态变化、核 形态，DNA合成，分裂速度，细胞大小，是否存在 特征性分化/成熟抗原，表面存在 酶，以及某些癌基因的激活)，在存在和 没有TPP。

This study seeks to identify alterations in immune cell function due to exposure to organophosphate compounds. These compounds, as a class, are used extensively in agricultural (pesticides, fungicides), industrial (plasticizers, additives, recovery agents), and in day-to-day applications (lawn and garden products, lubricants, varnishes). Previous studies have clearly demonstrated the neurotoxic action of these compounds; safe exposure levels based on these data have been determined. However, recent information suggests effects on cells of the immune system to occur at levels significantly lower than those required for neurotoxicity. The present study focuses on the effects of triphenyl phosphate, a 'model' organophosphate, on cells of the monocyte/macrophage lineage. These cells are essential to the induction and regulation of immune reactivity; they also play a crucial effector role in immune responses and are important in normal development and repair processes. Evidence from in vivo and in vitro studies suggests the monocyte/macrophage cell lineage to be sensitive to organophosphate compounds. The proposed studies, using control and treated murine and human primary cell cultures and cell lines, investigate three specific areas where preliminary work has shown macrophage function to be altered by TPP and similar compounds. These include: (1) Alteration in parameters critical to antigen presentation and cell-to-cell cooperation. Surface antigen expression will be determined by fluorescence activated cell sorting (FACS), light and electron microscopic immunocytochemistry, and ELISA. Correlative IL-1, phagocytosis and antigen presentation assays will be performed. (2) Effects of TPP on esterase enzyme activity in mature cells and cells at different stages in the differentiation pathway. Light and fluorescence microscopy and FACS analysis of esterase activity will be done. Correlative FACS analysis of esterase activity, surface antigen expression, and cell size and complexity will be performed. Recently developed procedures for simultaneous observation of surface antigens and esterase activity will be employed, as will studies on the effects of TPP on extracted esterase isoenzymes. (3) Alteration in precursor cell differentiation and gene expression due to TPP exposure. Precursor cell fines, which can be induced to differentiate to mature monocyte/macrophage-like cells, will be examined for differentiation-specific markers (e.g., morphologic changes, nuclear morphology, DNA synthesis, rate of division, cell size, presence of characteristic differentiation/maturation antigens, presence of surface enzymes, and activation of certain oncogenes), both in the presence and absence of TPP.