EFFECT OF PRENATAL CHLORDANE ON MACROPHAGE FUNCTION

产前氯丹对巨噬细胞功能的影响

• 批准号: 3250126
• 负责人: John B Barnett
• 金额: $ 19.35万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-06-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3250126
• 关键词: RNA biosynthesis; bioassay; chlordane; cytotoxicity; embryo /fetus toxicology; environmental toxicology; enzyme linked immunosorbent assay; genetic strain; histopathology; insecticide biological effect; laboratory mouse; macrophage; messenger RNA; molecular genetics; nuclear runoff assay; prenatal stress

DESCRIPTION: (Adapted from the investigator's abstract) The investigators have shown that prenatal exposure to the polychlorinated hydrocarbon pesticide, chlordane, affects the normal immune ontogeny. They recently found that these prenatally-exposed animals have a severe reduction in the ability of stem cells in the fetal liver, and in 100 and 200 day old bone marrow, to respond to granulocyte/macrophage-colony stimulating factor (GM-CSF) and to recolonize the spleens of irradiated animals (CFU-S) indicating that chlordane may be permanently affecting stem cells during ontogeny. Research is proposed to identify the stage in ontogeny initially affected, i.e., does chlordane have its effect as the pluripotent stem cell prior to its differentiation into a committed progenitor cell, determine the cell cycle stage affected by the chlordane in the target stem cell, and based on this information investigate the mechanistic causes of the defect(s). A goal is to more extensively define the model by determining the timing of the chlordane effects during gestation; determining the fetal-maternal tissue(s) affected by the chlordane; and determining whether the defect can be passed to the progeny (F2) of the affected F1 generation. A functional deficit in macrophages could account for previous reported decreases in DTH, or the consequences of a reduced DTH, as the macrophage plays a large role in the efferent phase of DTH reaction. A plan therefore is to thoroughly examine the macrophage for possible defects by examining the activation pathway of the macrophage at 100 days of age to determine the stage affected, and determine the intracellular location and nature of the defect by examining immunological, biochemical and molecular biological techniques.

描述：(改编自调查人员摘要)调查人员 已经表明，产前接触多氯碳氢化合物 杀虫剂氯丹会影响正常的免疫个体发育。他们最近 研究发现，这些产前接触过的动物体内的 胚胎肝脏、100日龄和200日龄骨骼中干细胞的能力 骨髓对粒细胞/巨噬细胞集落刺激因子的反应 (GM-CSF)和重新克隆受照射动物的脾(CFU-S) 表明氯丹可能会永久性地影响干细胞 个体发育学。建议进行研究，以初步确定个体发育的阶段 受影响，即氯丹是否具有作为多能干细胞的作用 在分化为定向祖细胞之前，确定 靶干细胞中受氯丹影响的细胞周期阶段，以及 基于这些信息，调查了 缺陷(S)。目标是更广泛地定义模型，通过确定 在怀孕期间氯丹效应的时间；确定 受氯丹影响的胎儿-母体组织(S)；以及确定 缺陷可以遗传给受影响的F1代的后代(F2)。 巨噬细胞的功能缺陷可能是先前报道的原因 DTH降低，或DTH降低的后果，如巨噬细胞 在DTH反应的传出阶段起着重要作用。因此，制定了一个计划 是彻底检查巨噬细胞是否存在可能的缺陷 100日龄巨噬细胞激活途径的测定 影响的阶段，并决定了细胞内的位置和性质 通过免疫学、生化和分子生物学检查发现的缺陷 技巧。