CARDIOTOXICITY OF STREPTOCOCCAL PYROGENIC EXOTOXIN

该研究研究了A组链球菌 致热外毒素（SPES）使宿主易于心肌损伤， 致命的休克由其他代理人，也许最重要的属性，这些 毒素 将尝试确定毒素上的位点（表位 其结合抗体，包括中和免疫系统细胞， 心脏细胞，试图确定生物学所需的区域， 毒性 SPE有能力引起猩红热，一种中毒性休克 综合征样疾病，并可能有助于早期事件， 风湿热、其他自身免疫性疾病和血管性疾病的发展 生活中的疾病 研究阐明增强的机制 心肌损伤和休克的易感性将在几个 方向 将检测A型和C型SPE作为代表性外毒素 特异性结合心脏和肝脏细胞的能力， 脾细胞 然后将研究分离的心脏和肝细胞， 最有可能的增强目标。 单独的外毒素， 并与内毒素（代表性的第二种试剂）一起进行检测 破坏细胞膜完整性，改变大分子 合成，诱导白细胞介素1，并改变内毒素摄取， 解毒 确定靶细胞相互作用位点的研究， 抗体结合将在三个方向上进行。 单克隆抗体 针对SPE A和C的抗体将用于阻断生物活性。 蛋白水解酶、其他裂解剂和遗传技术将被广泛应用。 用于产生具有部分生物活性的毒素片段， 结合细胞和抗体的能力。

The research studies the mechanism(s) by which group A streptococcal pyrogenic exotoxins (SPES) predispose the host to myocardial damage and lethal shock by other agents, perhaps the most important property of these toxins. Attempts will be made to identify sites (epitopes) on the toxins which bind antibodies, including neutralizing, immune system cells and heart cells, in attempts to identify regions necessary for biological toxicity. The SPEs have the capacity to cause scarlet fever, a toxic-shock syndrome-like illness, and may contribute to the early events in development of rheumatic fever, other autoimmune diseases, and vascular diseases later in life. Research to elucidate the mechanism of enhanced susceptibility to myocardial damage and shock will proceed in several directions. SPE types A and C, as representative exotoxins, will be tested for capacity to bind specifically to heart and liver cells, and splenocytes. Isolated heart and liver cells will then be investigated as the most likely targets for enhancement. Exotoxins alone, in combination, and together with endotoxin (a representative second agent) will be tested for capacity to disrupt cell membrane integrity, alter macromolecular synthesis, induce interleukin 1, and alter endotoxin uptake and subsequent detoxification. Studies to identify sites for target cell interaction and antibody binding will proceed in three directions. Monoclonal antibodies against SPEs A and C will be used to block biological activities. Proteolytic enzymes, other cleavage agents, and genetic techniques will be used to generate toxin fragments with partial biological activities, capacities to bind cells and antibodies.