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可保护小鼠免受铜绿假单胞菌攻击的人源单克隆抗体。

Human monoclonal antibodies that protect mice against challenge with Pseudomonas aeruginosa.

作者信息

Zweerink H J, Gammon M C, Hutchison C F, Jackson J J, Lombardo D, Miner K M, Puckett J M, Sewell T J, Sigal N H

机构信息

Department of Immunology Research, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065-0900.

出版信息

Infect Immun. 1988 Aug;56(8):1873-9. doi: 10.1128/iai.56.8.1873-1879.1988.

Abstract

Lymphocytes from healthy volunteers and from cystic fibrosis patients were transformed with Epstein-Barr virus and cultured at a limiting dilution to generate lymphoblastoid cell lines that secreted human monoclonal antibodies specific for lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Three cell lines (RM5, FDD7, and 11F9) produced immunoglobulin M (IgM) antibody species that reacted specifically with P. aeruginosa Fisher immunotypes 2, 4, and 5, respectively, and with LPS extracted from these immunotypes. A fourth cell line (9H10) produced a single IgM antibody species that recognized P. aeruginosa immunotypes 3, 6, and 7 and LPS extracted from them. Monoclonal antibodies secreted by cell lines RM5, FDD7, and 11F9 protected neutropenic mice prophylactically against challenge with P. aeruginosa immunotypes 2, 4, and 5, and those secreted by 9H10 protected against P. aeruginosa immunotypes 3 and 6 but did not protect against immunotype 7. In vivo experiments indicated that antibodies protected mice against infection by increasing the rate of bacterial clearance.

摘要

从健康志愿者和囊性纤维化患者体内获取淋巴细胞,用爱泼斯坦-巴尔病毒进行转化,并在有限稀释条件下培养,以生成能分泌针对铜绿假单胞菌脂多糖(LPS)的人单克隆抗体的淋巴母细胞系。三个细胞系(RM5、FDD7和11F9)产生的免疫球蛋白M(IgM)抗体分别与铜绿假单胞菌费舍尔免疫型2、4和5以及从这些免疫型中提取的LPS发生特异性反应。第四个细胞系(9H10)产生一种单一的IgM抗体,可识别铜绿假单胞菌免疫型3、6和7以及从它们中提取的LPS。细胞系RM5、FDD7和11F9分泌的单克隆抗体可预防性保护中性粒细胞减少的小鼠免受铜绿假单胞菌免疫型2、4和5的攻击,9H10分泌的单克隆抗体可保护小鼠免受铜绿假单胞菌免疫型3和6的攻击,但不能保护免受免疫型7的攻击。体内实验表明,抗体通过提高细菌清除率来保护小鼠免受感染。

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