MOLECULAR PATHOLOGY OF LPS HOST-PROTEIN COMPLEXES

革兰氏阴性脓毒症后的内毒素休克是一种严重的 医疗问题，尤指烧伤或创伤受伤的病人。 低血压休克，凝血障碍，多器官衰竭，以及 与革兰氏阴性脓毒症相关的后续死亡 被证明是由细胞壁脂多糖(LPS)启动的 革兰氏阴性菌重新进入血液。最新研究 证明了一种新发现的急性期反应物的存在 在小鼠、大鼠、兔子和人类的血清中 几种类型的伤害。这一急性期的独特性质 反应物是它与内毒素结合。因此，血液动力学和 脂多糖的内毒素特性被改变。拟议的研究 其总体目标是了解后果和 脂多糖结合蛋白(LBP)-内毒素的性质 互动。因此，一个特定的目标是生物化学 LBP的表征及其化学计量、结构和性质 LBP-LPS络合物的性质。研究的这一部分将 包括LBP的氨基酸序列研究、光化学 LBP和内毒素的交联法确定LBP-内毒素的结合部位 LBP-LPS络合物的相互作用、动力学和平衡研究 形成和分解。另一个具体目标是 确定LBP-LBP对内毒素的影响。 形成了脂多糖复合体。这些研究将包括体外试验 细胞激活和体液调节系统的研究 通过内毒素和LBP-内毒素复合体以及对内毒素去向的研究 动物急性期及内毒素诱导能力的研究 发热及其他生理反应前后 与LBP络合。这项研究可能会建议治疗 革兰氏阴性败血症进展的干预方法 在内毒素与体液成分相互作用的早期阶段发生休克。

Endotoxic shock subsequent to gram negative sepsis is a serious medical problem, especially of burn or trauma injured patients. The hypotensive shock, coagulopathy, multiple organ failure, and consequent fatality associated with gram negative sepsis have been shown to be initialed by the cell wall lipopolysaccharides (LPS) of gram negative bacteria re?eased into the blood. Recent research has shown the existence of a newly recognized acute phase reactant in the sera of mice, rats, rabbits, and humans subsequent to several types of injury. The unique property of this acute phase reactant is that it binds to LPS. As a result, the hemodynamic and endotoxic properties oF the LPS are modifed. The proposed research has as its overall goals an understanding of the consequences and nature of the lipopolysaccharide binding protein (LBP)-LPS interaction. Thus, one specific aim is a biochemical characterization of LBP and the stoichiometry, structure, and properties of LBP-LPS complexes. This portion of the study will include amino acid sequencing studies of LBP, photochemical crosslinking of LBP and LPS to determine sites of LBP-LPS interaction, and kinetic and equilibrium studies of LBP-LPS complex formation and decomposition. An additional specific aim is to determine in what ways the endotoxicity of LPS is changed when LBP- LPS complexes are formed. These studies will include in vitro studies of the activation of cells and humoral mediation systems by LPS and LBP-LPS complexes, as well as studies of the fate of LPS in acute phase animals and studies of the ability of LPS to induce febrile and other physiological responses before and after complexation with LBP. This research may suggest therapeutic methods for intervention in the progress of gram negative septic shock at an early stage of LPS interaction with humoral components.