WATCHING TARGET CELL OXIDATION AND CYTOLYSIS

跨学科研究计划将直接观察活细胞 当它们氧化和溶解靶细胞时，免疫系统的反应。 氧化 和靶细胞的细胞溶解以前从未被观察到， 光学显微镜 新的生物和物理技术现在使这一点 可能 此外，效应细胞组织它们的细胞的方式， 将探索进行这些活动的质膜。 三 在这些研究中将采用模型靶点：1）绵羊红细胞，2） 8 E5细胞，其已被人免疫缺陷病毒感染，和3） 肿瘤细胞 中性粒细胞介导的IgG调理红细胞的氧化和细胞溶解 将通过Soret带透射光显微镜和曙红Y观察 标记方法，分别。 氧化分子的作用将是 使用慢性肉芽肿病中性粒细胞进行研究。 细胞表面 中性粒细胞Fc受体的分布之前，期间和之后的抗体- 将测定依赖性细胞毒性。 一系列类似的 实验将在C3双调理红细胞上进行， 补体受体CR 3。 将这些结果与溶细胞的 淋巴细胞的机制。 中性粒细胞和巨噬细胞介导的8 E5和肿瘤细胞的氧化 将被研究。 将标记有核靶细胞的胞质溶胶 用对氧化条件敏感的荧光化合物。 的 效应细胞表面Fc受体的特性 将在抗体依赖性细胞毒性期间研究氧化。 非抗体依赖性细胞毒作用中肿瘤靶点的氧化 也将被研究。

The interdisciplinary research program will directly observe living cells of the immune system as they oxidize and lyse target cells. The oxidation and cytolysis of target cells have never previously been observed by optical microscopy. New biological and physical technologies now make this possible. Furthermore, the manner in which effector cells organize their plasma membranes to carry out these activities will be explored. Three model targets will be employed in these studies: 1) sheep erythrocytes, 2) 8E5 cells, which have been infected by human immunodeficiency virus, and 3) tumor cells. Neutrophil-mediated oxidation and cytolysis of IgG-opsonized erythrocytes will be observed by Soret band transmitted light microscopy and eosin Y labeling methods, respectively. The role of oxidative molecules will be studied using chronic granulomatous disease neutrophils. The cell surface distribution of neutrophil Fc receptors before, during, and after antibody- dependent cellular cytotoxicity will be determined. A similar series of experiments will be conducted on C3bi-opsonized erythrocytes and the complement receptor CR3. These results will be compared to the cytolytic mechanism(s) of lymphocytes. The neutrophil- and macrophage-mediated oxidation of 8E5 and tumor cells will be studied. The cytosol of nucleated target cells will be labeled with fluorescent compounds that are sensitive to oxidative conditions. The properties of effector cell surface Fc receptors during target cell oxidation will be studied during antibody-dependent cellular cytotoxicity. The oxidation of tumor targets during antibody-independent cytotoxicity will also be studied.