MOLECULAR BASES OF INTERFERON-INDUCED FUNGISTATIS

干扰素诱导真菌抑制的分子基础

• 批准号: 3134721
• 负责人: DEXTER H HOWARD
• 金额: $ 16.66万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3134721
• 关键词: aminoacid metabolism; antifungal agents; colony stimulating factor; gel electrophoresis; histoplasmosis; host organism interaction; immunomodulators; interferons; intracellular parasitism; laboratory mouse; lipopolysaccharides; macrophage; methionine; microorganism growth; microorganism immunology; monokines; peptides; tissue /cell culture; tumor necrosis factor alpha

The overall goal of the work is to discover how the intracellular growth of the zoopathogenic fungus Histoplasma capsulatum is terminated within macrophages of a recovering host. Such knowledge would be useful in developing immune therapeutic strategies for controlling progressive, disseminated forms of histoplasmosis in which recovery is not the rule. The cells to be used are resident peritoneal macrophages from the C57BL/6 and C3H/HeJ strains of mice and macrophages from the permanent cell lines P338D,and IC-21. Soluble modulators to be studied initially are: Gamma Interferon (IFN-gamma), Lipopoly- saccharide (LPS), Tumor Necrosis Factor (TNF), and Granulocyte/macrophage-Colony Stimulating Factor (GM-CSF). The specific aims are: (1) to continue studies on the molecular bases for the fungistasis induced in macrophages by recombinant IFN-gamma. The experiments to be conducted will measure the transport, intracellular pool size, and catabolism of methionine, an amino acid whose availability can control intracellular growth of H. capsulatum; and (2) to continue and to augment studies on the ability of IFN-gamma alone and in combination with other immunomodulators to establish an antihistoplasma state with the different sorts of macrophages. The analyses will be conducted by: (i) measuring the intracellular growth and viability of H. capsulatum; (ii) separating by gel electrophoresis the unique peptides formed by IFN-gamma alone or in combination with other modulators; and (iii) assessing the potential role of the peptides in the induced fungistasis or fungicidal state of the macrophages.

工作的总体目标是发现细胞内如何 zOOPATHINEC组织囊肿的生长是 终止在恢复宿主的巨噬细胞中。 这样的知识 对于制定免疫治疗策略将很有用 控制渐进的，传播形式的组织胞浆症 哪个恢复不是规则。 要使用的细胞是来自居民的腹膜巨噬细胞 C57BL/6和C3H/HEJ菌株的小鼠菌株和巨噬细胞 永久性细胞系P338D和IC-21。 可溶性调节器 最初研究的是：伽马干扰素（IFN-Gamma），脂垄 糖（LPS），肿瘤坏死因子（TNF）和 粒细胞/巨噬细胞 - 色元刺激因子（GM-CSF）。 具体目的是：（1）继续研究分子 重组在巨噬细胞中诱导的局势的基础 ifn-gamma。 要进行的实验将测量 运输，细胞内池的大小和蛋氨酸分解代谢， 可用性可以控制细胞内生长的氨基酸 H. capsulatum; （2）继续并增强有关 单独使用IFN-gamma并与其他人结合的能力 免疫调节剂以建立一个抗组织状态 不同种类的巨噬细胞。 分析将通过： （i）测量H的细胞内生长和生存能力。 胶囊； （ii）通过凝胶电泳分离独特 由IFN-gamma形成的肽单独或与其他肽形成 调节器； （iii）评估肽的潜在作用 巨噬细胞的诱导局势或杀真菌状态。