TOXINS OF PERTUSSIS--ISOLATION, CHARACTERIZATION AND MECHANISMS OF ACTION

百日咳杆菌，一种常见的致病微生物 称为百日咳，会产生几种毒素(即百日咳毒素 (PT)和不耐热或皮肤坏死毒素)(见项目Z01 HD 01306) 它们似乎在生物体的发病机制中发挥着重要作用。PT， 此外，它是一种主要的保护性抗原，是一个很有前途的候选抗原 用于开发新的无细胞百日咳疫苗(见项目Z01 HD 01307)。目前的项目集中在阐明这些机制。 百日咳毒素与细胞相互作用并引起其多样性 药理作用。PT与其相互作用中的初始事件 细胞似乎是毒素的快速和本质上不可逆的结合 传给细胞。利用PT与胎球蛋白的相互作用作为模型，研究已经 已经进行了鉴定碳水化合物结构的研究， 百日咳毒素相互作用。PT的毒性作用是由毒素介导的 ADP-核糖部分从NAD到腺苷的催化转移 环化酶调节成分，Ni。PT的这一动作已被用作 探讨镍在细胞功能调节中的作用 特别强调那些参与免疫反应的细胞类型。 PT对淋巴样细胞的处理会导致不同的反应， 在发病机制中，PT起到干扰免疫的作用 回应。已经证明，用PT治疗可以阻止产生 细胞毒性T淋巴细胞(CTL)，并导致产生改变的 Interleukins。这些研究指出了PT在改变 免疫系统以允许持续感染的方式。 旨在阐明受以下因素影响的调节途径的研究 百日咳毒素的作用机制，可能会提供更多的洞察力 调节免疫反应的物质。

Bordetella pertussis, the microorganisms which cause the disease commonly known as whooping cough, produces several toxins (i.e., pertussis toxin (PT) and heat labile or dermonecrotic toxin) (see project Z01 HD 01306) which appear to play important roles in pathogenesis of the organism. PT, in addition, is a major protective antigen which is a promising candidate for the development of a new acellular pertussis vaccine (see project Z01 HD 01307). The current project concentrates on elucidating the mechanisms by which pertussis toxin interacts with cells and elicits its diverse pharmacologic actions. The initial event in the interaction of PT with cells appears to be a rapid and essentially irreversible binding of toxin to cells. Using the interaction of PT with fetuin as a model, studies have been conducted which identify the carbohydrate structure with which pertussis toxin interacts. The toxic action of PT is mediated by toxin catalyzed transfer of the ADP-ribose moiety from NAD to the adenylate cyclase regulatory component, Ni. This action of PT has been used as a probe to explore the role of Ni in regulation of cell function, with specific emphasis on those cell types involved in immune response. Treatment of lymphoid cells with PT results in diverse responses which establish that in pathogenesis, PT acts to interfere with the immune response. Treatment with PT has been shown to block the production of cytotoxic T-lymphocytes (CTL's) and results in altered production of the interleukins. These studies point to the importance of PT in altering the immune system in a manner which permits the continuance of infection. Studies aimed at elucidation of the regulating pathways, affected by pertussis toxin action, may provide greater insight into the mechanisms which modulate immune response.