ORGANOPHOSPHATE IMMUNOACTIVITY

这项研究旨在确定免疫细胞功能的改变， 接触有机磷酸盐化合物。 这些化合物，作为一类， 广泛用于农业（杀虫剂，杀菌剂），工业 （增塑剂，添加剂，回收剂），并在日常 应用（草坪和花园产品、润滑剂、清漆）。 先前 研究已经清楚地证明了这些化合物的神经毒性作用。 根据这些数据确定了安全接触水平。 然而，最近的信息表明， 系统发生的水平大大低于所需的 神经毒性 本研究的重点是三苯 磷酸盐，一种“模型”有机磷酸盐，对单核细胞/巨噬细胞的细胞 脉 这些细胞对于诱导和调节 免疫反应性;它们也在免疫反应中起关键效应子作用。 反应，并在正常发育和修复过程中发挥重要作用。 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. 使用对照和经处理的小鼠和人原发性 细胞培养和细胞系，研究三个特定领域， 初步研究表明，巨噬细胞功能被TPP改变， 类似的化合物。 这些问题包括：（1）关键参数的改变 抗原呈递和细胞与细胞的合作。 表面抗原 表达将通过荧光激活细胞分选来确定 流式细胞术（FACS）、光镜和电镜免疫细胞化学和ELISA。 相关的IL-1、吞噬作用和抗原呈递试验将在 执行。(2)TPP对成熟细胞酯酶活性的影响 以及分化途径中不同阶段的细胞。 光和 荧光显微镜和流式细胞仪分析酯酶活性将是 完了 酯酶活性、表面抗原的相关性FACS分析 表达式，以及单元格大小和复杂性。 最近 开发了同时观察表面抗原的程序， 将采用酯酶活性，以及对TPP影响的研究 提取的酯酶同工酶。(3)前体细胞改变 细胞分化和基因表达的影响。 前体细胞 细粉，可以诱导分化成熟 单核细胞/巨噬细胞样细胞，将检查 分化特异性标记（例如，核形态学变化 形态学、DNA合成、分裂速率、细胞大小、 特征性分化/成熟抗原，存在表面 酶和某些致癌基因的激活），无论是在存在和 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.