ASPERGILLUS FUMIGATUS COMPLEMENT INHIBITOR (CI)

烟曲霉补体抑制剂 (CI)

• 批准号: 2057053
• 负责人: RONALD G WASHBURN
• 金额: $ 6.72万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2057053
• 关键词: Aspergillus; aspergillosis; autoradiography; chemical binding; complement inhibitors; enzyme linked immunosorbent assay; gas chromatography; high performance liquid chromatography; human tissue; laboratory mouse; laboratory rabbit; lipids; mass spectrometry; mutant; nuclear magnetic resonance spectroscopy; properdin; radiotracer; thin layer chromatography; ultraviolet radiation; virulence

Aspergillus CI was the first described complement inhibitor produced by a fungus which causes human disease. The inhibitor might enhance pathogenicity of Aspergillus in the human host by impairing opsonization and diminishing generation of the chemoattractant for polymorphonuclear neutrophils and monocytes, C5a. Now in press is the demonstration that polar fungal lipids which comigrate during thin layer chromatography with phosphatidylserine/phosphatidylinositol and phosphatidylethanolamine contribute to the inhibitory activity of CI. In addition, the observation has recently been made that properdin, a component of the alternative pathway C3 convertase, is able to completely obliterate CI's activity. During the funding period, inhibitory lipid(s) from preparative TLC will be identified by GC mass spectroscopy, NMR, and gas-liquid chromatography. Binding between (125)I-properdin and polar Aspergillus lipids will be assessed using a combination of TLC and autoradiography. In vivo production of relevant CI lipid(s) will be examined using labeled anti-CI IgG F(ab')2 in a mouse model of invasive aspergillosis , and in available human tissues. Sera of infected mice and of patients with various forms of aspergillosis will be checked for the presence of CI lipid(s) by ELISA. A CI- mutant will be selected following ultraviolet irradiation of CI+ wild-type A. fumigatus. This mutant will allow an assessment of the in vivo significance of CI by comparing LD50s for inhaled inocula of both isolates in the mouse model.

曲霉CI是由A产生的第一个描述的补体抑制剂 引起人类疾病的真菌。 抑制剂可能会增强 人类宿主中曲霉菌的致病性通过损害调子化 并减少了多形核的化学吸收剂的产生 中性粒细胞和单核细胞，C5A。 现在在印刷中是示范 极性真菌脂质，在薄层色谱期间与 磷脂酰丝氨酸/磷脂酰肌醇和磷脂酰乙醇胺 有助于CI的抑制活性。 另外，观察 最近已将替代方案的组成部分提出 途径C3转化酶，能够完全消除CI的活动。 在资金期间，制剂TLC的抑制性脂质将是 通过GC质谱，NMR和气体色谱法鉴定。 （125）I-丙丁蛋白和极性曲霉脂质之间的结合将是 使用TLC和放射自显影的组合进行评估。 体内 将使用标记的抗CI检查相关的CI脂质的产生 IgG F（AB'）2在侵入性曲霉病的小鼠模型中，可用 人体组织。 感染小鼠的血清和各种形式的患者的血清 ELISA将检查曲霉病是否存在CI脂质（S）。 一个 CI+紫外线辐射后将选择CI-突变体 野生型A. Fumigatus。 该突变体将允许评估IN 通过比较两者的吸入接种的LD50s的体内显着性 鼠标模型中的分离物。