MOLECULAR MECHANISMS OF ORGANOPHOSPHATE IMMUNOTOXICITY

细菌中两种杂质抑制免疫的分子机制 有机磷农药、马拉硫磷、乙酰甲胺磷和敌硝硫磷， O，O，S-三甲基硫代硫酸酯和O，S，S-三甲基 二硫代磷酸，将被检测。宏页，通过单元格 分离和重建实验已经被证明是 OOS-TMP治疗对淋巴样细胞影响最大。交通堵塞的原因是 急性给药后巨噬细胞的成熟 将确定OOS-TMP。研究将包括巨噬细胞的变化 细胞表面标志物Ia、Mac-1、Mac-2和F4/80，功能活性和 分泌性产品。结构类似物OSS-TMP的抑制作用 关于细胞溶解效应器的功能将使用 功能定义的细胞毒性T淋巴细胞(CTL)和其他细胞溶解 效应细胞。将阻断小鼠CTL功能的部位(S) 使用共轭形成和钙脉冲技术测定。这个 将使用放射性标记的OSS-TMP和 生化分析。此外，一种改装的比色法 (染料减少)对细胞活力的适用性将进行研究 作为细胞毒活性和细胞抑制力的筛选试验 环境毒物。这项检测可能是标准的替代方法。 台盼蓝拒染法检测细胞活力。

The molecular mechanisms of immune suppression by two impurities in the organosphosphate pesticides, malathion, acephate and fenitrothion, O,O,S-trimethyl phosphorothioate (OOS-TMP) and O,S,S-trimethyl phosphorodithioate, will be examined. Macrophaages, through cell separation and reconstitution experiments, have been shown to be the lymphoid cell most affected by OOS-TMP treatment. The blockage in the maturation of macrophages which occurs following acute administration of OOS-TMP will be identified. Studies will include changes in macrophage cell surface markers, Ia, Mac-1, Mac-2 and F4/80, functional activity and secretory products. The inhibitory effect of a structural analog OSS-TMP on cytolytic effector function will be examined in detail using functionally defined cytotoxic T lymphocytes (CTL) and other cytolytic effector cells. The site(s) of the blockade of murine CTL function will be determined using conjugate formation and Ca2+ pulse techniques. The molecular sites will be identified using radiolabelled OSS-TMP and biochemical analyses. In addition, an adaptation of a colorimetric assay (dye reduction) for cell viability will be investigated for its suitability as a screening assay for the cytotoxic and cytostatic activities of environmental toxicants. This assay may be an alternative to the standard trypan blue exclusion method for assessing cell viability.