Parent J B, Gazzano-Santoro H, Wood D M, Lim E, Pruyne P T, Trown P W, Conlon P J
Department of Preclinical Science, XOMA Corporation, Berkeley, California 94710.
Circ Shock. 1992 Sep;38(1):63-73.
The murine monoclonal IgM antibody E5 has been shown to significantly reduce the mortality and morbidity of patients with Gram-negative sepsis in a multicenter randomized placebo-controlled clinical trial. The in vitro binding characteristics of monoclonal antibody (mAb) E5 were studied using highly purified smooth lipopolysaccharide (LPS) isolated from a variety of clinically relevant, wild-type Gram-negative bacteria. Using a sensitive antibody-capture assay which involves immobilized mAb E5 and a chromogenic Limulus amebocyte lysate (LAL) LPS-detection system, mAb E5 was shown to bind to all 15 smooth LPS preparations tested, including LPS isolated from Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Serratia and Yersinia species. When LPS was fractionated according to size by size-exclusion chromatography, mAb E5 was shown to bind to smooth LPS molecules that have long as well as short O-polysaccharide chains. These results confirm and extend those reported previously and demonstrate that the anti-lipid A mAb E5 binds specifically to a diverse spectrum of smooth LPS isolated from wild-type Gram-negative bacteria.
在一项多中心随机安慰剂对照临床试验中，鼠单克隆IgM抗体E5已被证明可显著降低革兰氏阴性菌败血症患者的死亡率和发病率。使用从多种临床相关的野生型革兰氏阴性菌中分离出的高度纯化的光滑脂多糖（LPS）研究了单克隆抗体（mAb）E5的体外结合特性。使用一种灵敏的抗体捕获测定法，该方法涉及固定化的mAb E5和显色鲎试剂（LAL）LPS检测系统，结果表明mAb E5能与所测试的所有15种光滑LPS制剂结合，包括从大肠杆菌、克雷伯菌、变形杆菌、假单胞菌、沙门氏菌、沙雷氏菌和耶尔森氏菌属分离出的LPS。当通过尺寸排阻色谱法按大小对LPS进行分级分离时，结果表明mAb E5能与具有长O多糖链和短O多糖链的光滑LPS分子结合。这些结果证实并扩展了先前报道的结果，表明抗脂质A单克隆抗体E5能特异性结合从野生型革兰氏阴性菌中分离出的多种光滑LPS。
