Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies.
Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies.
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使用人单克隆 IgM 抗体预防革兰氏阴性菌血症和内毒素血症。
DOI：
10.1073/pnas.82.6.1790
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发表时间：
1985
影响因子：
11.1
通讯作者：
Braude,AI
中科院分区：
文献类型：
--
作者：
Teng,NN;Kaplan,HS;Hebert,JM;Moore,C;Douglas,H;Wunderlich,A;Braude,AI
用致敏的人脾脏B淋巴细胞与异骨髓瘤细胞融合制备了能产生抗细菌脂多糖（LPS）的人单克隆IgM抗体（mab）的杂交瘤。这些脾细胞来自于在霍奇金病分期期间接受脾切除术的患者，他们接种了缺乏O抗原侧链的大肠杆菌J5突变体。这种缺陷暴露了核心低聚糖，这是所有革兰氏阴性细菌的LPS所共有的。单克隆抗体与来自多种不相关的革兰氏阴性细菌的内毒素发生强烈的交叉反应。该单克隆抗体对小鼠皮肤Shwartzman反应中的LPS和致死性革兰氏阴性菌血症也有很强的保护作用。这些结果表明，抗LPS内毒素的单克隆IgM可以在体内中和其毒性，可能对革兰氏阴性菌血症患者的治疗有价值。对其中一个杂交瘤克隆A6（H4C5）的分析表明，IgM单抗针对的是共价结合的脂质A，这是LPS中最保守、变化最小的结构元件。
Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells. The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the J5 mutant of Escherichia coli, which is deficient in O antigenic side chains. This deficiency exposes the core oligosaccharide, common to LPS of all Gram-negative bacteria. The mAbs cross-reacted strongly with endotoxins from a wide range of unrelated species of Gram-negative bacteria. The mAbs also gave strong protection against LPS in the dermal Shwartzman reaction and against lethal Gram-negative bacteremia in mice. These findings indicate that monoclonal IgM against LPS endotoxin can neutralize its toxicity in vivo and might be valuable for treatment of patients with Gram-negative bacteremia. Analysis of one of the hybridoma clones, A6(H4C5), showed that the IgM mAb is directed against the covalently bound lipid A, which represents the most conservative and least variable structural element of LPS.