Lazaron Victor, Dunn David L
Department of Surgery, University of Minnesota, 420 Delaware Street SE, Box 195, Mayo Memorial Building, Minneapolis, Minnesota 55455, USA.
World J Surg. 2002 Jul;26(7):790-8. doi: 10.1007/s00268-002-4054-4. Epub 2002 Apr 15.
The development of new therapies for the treatment of gram-negative bacterial sepsis has been the focus of extensive investigation. Molecular and cellular biologic techniques have led to important advances, including (1) identification of naturally occurring lipopolysaccharide (LPS)-binding proteins; (2) generation of novel LPS-binding antibodies, proteins, and peptides; and (3) characterization of the molecular determinants of LPS binding. In composite, these advances have facilitated comprehension of the manner in which gram-negative bacterial infection and concurrent endotoxemia exert detrimental effects on the mammalian host. The purpose of this review was to examine recent information regarding molecular determinants of LPS binding and the initial cellular signal transduction events, which lead to the local and systemic cytokine response and sepsis syndrome. Concurrently, the status of studies examining the effects of various endotoxin antagonists is reviewed. Data from these studies provide an indication of potential sites for therapeutic intervention as well as increasingly detailed understanding of the molecular mechanism of endotoxin antagonism. Taken together, these advances can be expected to further the development of the next generation of novel, adjuvant therapies for the treatment of sepsis syndrome caused by gram-negative bacterial infection and endotoxemia.
开发治疗革兰氏阴性菌败血症的新疗法一直是广泛研究的重点。分子和细胞生物学技术取得了重要进展，包括：（1）鉴定天然存在的脂多糖（LPS）结合蛋白；（2）产生新型LPS结合抗体、蛋白和肽；（3）表征LPS结合的分子决定因素。综合起来，这些进展有助于理解革兰氏阴性菌感染和并发内毒素血症对哺乳动物宿主产生有害影响的方式。本综述的目的是研究有关LPS结合的分子决定因素以及导致局部和全身细胞因子反应及败血症综合征的初始细胞信号转导事件的最新信息。同时，对研究各种内毒素拮抗剂作用的研究现状进行了综述。这些研究的数据表明了治疗干预的潜在位点，并对内毒素拮抗作用的分子机制有了越来越详细的了解。综上所述，这些进展有望推动新一代新型辅助疗法的开发，用于治疗由革兰氏阴性菌感染和内毒素血症引起的败血症综合征。
