A STREPTOCOCCAL INACTIVATOR OF HUMAN CHEMOATTRACTANTS

这个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的倾向的基础和 评估一种新发现的链球菌灭活剂的重要性 补体介导的趋化作用，称为SCFI，对这一过程。这个 炎症的主要趋化因子--补体血清蛋白C5a 过程中，被相关的多肽酶活性特异性地切割 与SCFI合作。这里提出的研究将进一步定义 这种独特的链球菌多肽酶。分离提纯程序 将使用常规柱层析进行优化，并且高 压力层析法。用纯化的酶进行实验将 评估这一因素在链球菌毒力中的作用 影响链球菌对吞噬的抵抗力，协助 是粘膜组织定植还是延缓炎症反应？老鼠 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。M型的缺失 这种蛋白的特异性使其成为链球菌的潜在候选者 疫苗。这种可能性将通过对动物进行免疫来测试 纯化的SCFI。各种链球菌感染的动物模型将被 试过了。人类对SCFI的免疫学反应将由以下因素决定 健康人和康复者血清中抗体的定量检测 用间接酶联免疫吸附试验检测。

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.