A STREPTOCOCCAL INACTIVATOR OF HUMAN CHEMOATTRACTANTS

人类化学引诱剂的链球菌灭活剂

• 批准号: 3129488
• 负责人: PAUL Patrick CLEARY
• 金额: $ 2.07万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1989-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129488
• 关键词: bactericidal immunity; cell aggregation; chemotaxis; chromatography; complement inhibitors; enzyme linked immunosorbent assay; enzyme mechanism; glomerulonephritis; high performance liquid chromatography; human tissue; immunochemistry; inflammation; laboratory mouse; laboratory rabbit; leukocytes; microorganism immunology; molecular pathology; peptidases; phagocytosis; protease inhibitor; protein structure; virulence

The primary goal of this project is to better understand the biochemical basis for the propensity of group A streptococci to cause human disease and to evaluate the importance of a newly discovered streptococcal inactivator of complement mediated chemotaxis, designated SCFI, to this process. The human complement serum protein C5a, the primary chemotaxin of inflammatory processes, is specifically cleaved by the peptidase activity associated with SCFI. Studies proposed here will further define the specificity of this unique streptococcal peptidase. Isolation and purification procedures will be optimized employing conventional column chromatography, and high pressure chromatographic methods. Experiments with purified enzyme will evaluate the role of this factor in streptococcal virulence; does it influence the resistance of streptococci to phagocytosis, assist colonization of mucosal tissues or retard the inflammatory response? Mice and rabbits will be used for these experiments. Antisera able to neutralize SCFI activity will be tested for the potential to alter virulence of various streptococcal serotypes. The lack of M type specificity makes this protein a potential candidate for a streptococcal vaccine. This possibility will be tested by immunization of animals with purified SCFI. Various animal models of streptococcal infection will be tried. The immunological response to SCFI in humans will be determined by quantitating antibody in sera from healthy and convalescent individuals with an indirect ELISA assay.

该项目的主要目标是更好地了解生物化学 A组链球菌引起人类疾病倾向的基础， 评价一种新发现的链球菌灭活剂的重要性 补体介导的趋化性，指定SCFI，这一过程。 的 人补体血清蛋白C5 a，炎症的主要趋化因子 过程中，特异性裂解的肽酶活性相关 关于SCFI 本文提出的研究将进一步确定 这种独特的链球菌肽酶 分离和纯化程序 将采用常规柱色谱法进行优化， 压力色谱法 纯化酶的实验将 评估该因子在链球菌毒力中的作用;是否 影响链球菌对吞噬作用的抵抗力， 粘膜组织定植或延缓炎症反应？ 小鼠 兔子将被用于这些实验。 抗血清能够 将测试中和SCFI活性是否有可能改变 各种链球菌血清型的毒力。 缺少M型 特异性使该蛋白质成为链球菌感染的潜在候选者。 疫苗 这种可能性将通过以下动物免疫来测试： 纯化的SCFI。 将研究链球菌感染的各种动物模型。 试过了 人体对SCFI的免疫应答将通过以下方法确定： 对健康和恢复期个体血清中的抗体进行定量 间接ELISA检测。