INTERACTION OF LIPOPOLYSACCHARIDES WITH SERUM PROTEINS

内毒素内毒素(LPS)，由于其功能 定位于革兰氏阴性杆菌外膜， 在细菌与宿主的相互作用中起着关键作用 防御。这些交互中最重要的一个是与 血清蛋白质，尤其是补体系统的蛋白质。 脂多糖的结构决定因素被认为是 在确定革兰氏阴性杆菌的敏感性或抵抗力方面至关重要 细菌对血清补体的溶解作用。同样 重要的是潜在的病理生理效应 通过血清后细菌释放的内毒素 细菌溶解，包括休克、低血压和播散性 血管内凝血。尽管有众多的血清因素 据报道，内毒素的解毒活性既包括 这些因素及其作用机制仍不明确。 这项提案中概述的实验旨在 研究其对内毒素特异性多糖结构的影响 对内毒素与补体和补体的相互作用 非补体血清蛋白。在这些研究中， 大分子内毒素中含有的特异性内毒素决定簇 聚集体将通过操纵内毒素亚单位而变化 组成。专门构建的脂多糖制剂将 用来研究内毒素结构的机制 调节经典或替代的激活 补体途径。在这些实验中，提纯 两种途径的补体成分将被用来评估 补体成分相互作用的直接调控 特定的内毒素结构。这些研究将增加 对结构参数的理解 组件c1和c3，用于区分自我和非我。 将广泛使用放射性碘标记的可光激活脂多糖 研究与内毒素有亲和力的血清成分 它可以与内毒素结合并改变其生物学活性。蛋白质 经脂多糖交联鉴定的正常人血清的 以生化和免疫学分析为特点。在……里面 此外，还将测试这些蛋白质的抑制能力。 LPS介导的变形细胞裂解物(LAL)凝集。 识别内毒素失活因子可以允许 开发潜在有用的诊断和治疗方案 内毒素血症的治疗。

Endotoxic lipopolysaccharides (LPS), by virtue of their functional localization on the outer membrane of gram negative bacteria, play a pivotal role in the interaction of the bacterium with host defenses. One of the most important of these interactions is with serum proteins, particularly those of the complement system. Structural determinants of LPS have been recognized to be critical in defining sensitivity or resistance of gram negative bacteria to the lytic effects of serum complement. Equally important are the potential pathophysiological effects mediated by endotoxic LPS released from the bacterium following serum bacteriolysis, which include shock, hypotension and disseminated intravascular coagulation. In spite of the numerous serum factors reported to detoxify the endotoxic activities of LPS both the factors and their mechanism of action remain ill defined. The experiments outlined in this proposal have been designed to investigate the influence specific LPS polysaccharide structures have upon the interactions between LPS and both complement and non-complement serum proteins. For these studies the levels of specific LPS determinants contained within macromolecular LPS aggregates will be varied by manipulating LPS subunit composition. Specifically constructed LPS preparations will be used to investigate the mechanisms by which LPS structures regulate the activation of both the classical or alternative pathways of complement. For these experiments, purified complement components of both pathways will be used to assess directly the modulation of complement component interactions by specific LPS structures. These studies will increase the understanding of the structural parameters which allow components C1 and C3 to descriminate between self and non-self. Extensive use will be made of a radioiodinated photoactivable LPS derivitive to study serum components with an affinity for LPS which could bind LPS and alter its biological activities. Proteins of normal human serum identified by LPS crosslinking will be characterized by biochemical and immunological analysis. In addition, these proteins will be tested for their capacity to inhibit LPS mediated coagulation of Limulus ameobocyte lysates (LAL). Identification of LPS inactivating factors could allow for the development of potentially useful protocols for the diagnosis and treatment of endotoxemia.