MECHANISMS OF HUMAN BASOPHIL & MAST CELL DESENSITIZATION

这些研究的目的是阐明人类免疫缺陷的机制 嗜碱性粒细胞和肥大细胞脱敏。这样做的目的是理解 人嗜碱性粒细胞和肥大细胞介质释放的基本机制 为未来的过敏治疗提供了一个坚实的框架 疾病是有根据的。介体释放机构的一个方面是 这些细胞的自我调节能力通过称为 脱敏，正是在这方面，我们将集中努力。 本文针对四个方面进行研究。 1)阐明了二异丙基氟磷酸盐的抑制机制 脱敏 2)明确抗原和IgE的大规模聚集在 促进脱敏 3)比较肥大细胞脱敏和嗜碱性粒细胞脱敏 4)确定脱敏对两个已知激活事件的影响 生物化学、钙通量与磷脂周转 DFP已被发现可以抑制嗜碱性粒细胞的脱敏并增强 组胺释放支持脱敏调节的概念 放手。建议的研究将使用放射性标记的DFP或DFP 类似物来分离参与脱敏的酶(S)。 以往的研究表明，细胞表面IgE抗原的大小 聚集体决定了细胞介体的释放和特征 脱敏。证实这一假设的实验包括 比较几种定义明确的抗原的诱导能力 脱敏。结合分析和显微荧光 将使用光漂白技术来表征表面IgE 在这些抗原的影响下重新分布。 肥大细胞在过敏性疾病的病理生理学中起着中心作用。他们 现在可以提纯到近乎均一的水平。建议进行的研究将 确定在这些细胞中是否发生了非特异性脱敏 它们在刺激和刺激过程中如何处理抗原-IgE聚集体 脱敏。 以往的研究表明，细胞表面IgE抗原的大小 聚集体决定了细胞介体的释放和特征 脱敏。证实这一假设的实验包括 比较几种定义明确的抗原的诱导能力 脱敏。结合分析和显微荧光 将使用光漂白技术来表征表面IgE 在这些抗原的影响下重新分布。 肥大细胞是过敏性疾病病理生理学的中心。他们 现在可以提纯到近乎均一的水平。建议进行的研究将 确定在这些细胞中是否发生了非特异性脱敏 它们如何在刺激过程中处理抗原-IgE聚集体 去迷信。 最后，我们建议进行一些研究，以调查 肥大细胞的钙转运和磷脂转换 嗜碱性细胞。然后将检查脱敏的效果。

The purpose of these studies is to elucidate the mechanisms of human basophil and mast cell desensitization. The intention is to understand the basic mechanisms of humanbasophil and mast cell mediator release in hopes of providing a firm framework on which future therapies for allergic disease can be based. One aspect of the mediator release mechanism is these cells' capacity for autoregulation through the process termed desensitization, and it is on this aspect which we will focus our efforts. Four areas are targeted for study. 1) elucidating the mechanism by which diisopropylfluorophosphate inhibits desensitization 2) defining the role of large scale aggregation of antigen and IgE in promoting desensitization 3) comparing mast cell and basophil desensitization 4) determining the effects of desensitization on two known activation event biochemistries, calcium flux and phospholipid turnover DFP has been found to inhibit basophil desensitization and enhances histamine release supporting the concept that desensitization regulates release. Studies are proposed which will use radiolabeled DFP or DFP analogs to isolate the enzyme(s) involved in desensitization. Previous studies suggested that the size of cell surface IgE-antigen aggregates determine the characteristics cell mediator release and desensitization. Experiments to substantiate this hypothesis involve comparing several well defined antigens for their ability to induce desensitization. Binding assays and microscopic fluorescent photo-bleaching techniques will be employed to characterize surface IgE redistribution under the influence of these antigens. Mast cells are central to the pathophysiology of allergic diseases. They can now be purified to near homogeneity. Studies are proposed which will determine whether non-specific desensitization occurs in these cells and how they process antigen-IGE aggregates during stimulation and desensitization. Previous studies suggested that the size of cell surface IgE-antigen aggregates determine the characteristics cell mediator release and desensitization. Experiments to substantiate this hypothesis involve comparing several well defined antigens for their ability to induce desensitization. Binding assays and microscopic fluorescent photo-bleaching techniques will be employed to characterize surface IgE redistribution under the influence of these antigens. Mast cells are central to the pathopysiology of allergic diseases. They can now be purified to near homogeneity. Studies are proposed which will determine whether non-specific desensitization occurs in these cells and how they process antigen-IgE aggregates during stimulation and desenstitization. Finally, studies are proposed which will investigate the occurrence of calcium translocation and phospholipid turnover in both mast cells and basophils. The effect of desensitization will then be examined.