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，特别是烧伤或创伤受伤的病人。 休克，凝血障碍，多器官衰竭， 与革兰氏阴性脓毒症相关的后续死亡率已经 显示由细胞壁脂多糖（LPS）起始 革兰氏阴性菌RE？融入血液。 最近的研究 已经表明存在一种新发现的急性期反应物 在小鼠、大鼠、兔和人的血清中， 几种类型的伤害。 这种急性期的独特性质 反应物是它结合到LPS。 结果，血流动力学和 LPS的内毒素性质被改变。 拟议研究 其总体目标是了解后果， 脂多糖结合蛋白（LBP）-LPS的性质 互动 因此，一个具体的目标是生物化学 LBP的表征和化学计量，结构， LBP-LPS复合物的性质。 本部分研究将 包括LBP氨基酸测序研究、光化学 LBP和LPS的交联以确定LBP-LPS的位点 LBP-LPS复合物相互作用、动力学和平衡研究 形成和分解。 另一个具体目标是 确定当LBP时LPS的内毒素以何种方式改变- 形成LPS复合物。 这些研究将包括体外 细胞激活和体液调节系统的研究 通过LPS和LBP-LPS复合物，以及LPS命运的研究， 在急性期动物和LPS诱导的能力的研究 发热和其他生理反应前后 与LBP络合。 这项研究可能表明， 革兰氏阴性脓毒症进展中的干预方法 在LPS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.