Raponi Giammarco, Ghezzi M Cristina, Lun Maria T, Bigotti Giulio, Natali Pier G, Mancini Carlo
Institute of Microbiology, University of Rome 'La Sapienza' Ple Aldo Moro 5, 00185 Rome, *Department of Pathology, Catholic University of Rome 'S. Cuore', Lg. A. Gemelli, 1 00167 Rome and †Immunology Laboratory, 'Regina Elena' Cancer Institute, Via delle messi d'oro, Rome, Italy.
J Med Microbiol. 2000 Mar;49(3):253-260. doi: 10.1099/0022-1317-49-3-253.
Murine monoclonal antibodies (MAbs) MT1F and ARM1-4, recognising proteins on the surface of untreated Escherichia coli O6:K-, protected 100% of mice challenged intraperitoneally with 2 x LD50 of the same strain. MAb MT1F protected 70% of animals challenged with 2 x LD50 of E. coli O111:B4, whereas ARM1-4 gave complete protection. Lower survival was observed in mice given either MAb and challenged with E. coli O128:K-, with values ranging from 30 to 42%. However, the protection afforded against E. coli O111:B4 and E. coli O128:K- was significantly improved when the mice were pre-treated with a mixture of the two MAbs. Control mice, pre-treated with unrelated ascitic fluid and challenged with any of the E. coli serotypes, showed 100% mortality and organ histological lesions resembling those of the early stages of septic shock. The mice had high levels of circulating endotoxin and tumour necrosis factor-alpha (TNF-alpha) at 90 min after challenge. In contrast, mice treated with MAbs and surviving the infection displayed moderate histological lesions, enhanced bacterial clearance and lower serum levels of TNF-alpha, despite circulating endotoxin levels that were higher than in the control group. Protection by the MAbs was probably due to the prevention of the bacterial spread to organs and of the cascade of events leading to septic shock. This occurred in spite of the presence of high levels of circulating endotoxin.
鼠单克隆抗体（MAb）MT1F和ARM1 - 4可识别未处理的大肠杆菌O6:K - 表面的蛋白质，在用2倍半数致死剂量（LD50）的同一菌株进行腹腔注射攻击时，能保护100%的小鼠。MAb MT1F在用2倍LD50的大肠杆菌O111:B4攻击时，能保护70%的动物，而ARM1 - 4则能提供完全保护。在用任一单克隆抗体处理并受到大肠杆菌O128:K - 攻击的小鼠中，存活率较低，范围在30%至42%之间。然而，当小鼠用两种单克隆抗体的混合物进行预处理时，对大肠杆菌O111:B4和大肠杆菌O128:K - 的保护作用显著提高。用无关腹水进行预处理并受到任何一种大肠杆菌血清型攻击的对照小鼠，死亡率为100%，且器官组织学病变类似于脓毒性休克早期阶段的病变。在攻击后90分钟，这些小鼠的循环内毒素和肿瘤坏死因子 - α（TNF - α）水平很高。相比之下，经单克隆抗体处理并在感染中存活的小鼠，尽管循环内毒素水平高于对照组，但组织学病变较轻，细菌清除能力增强，血清TNF - α水平较低。单克隆抗体的保护作用可能是由于防止了细菌向器官扩散以及防止了导致脓毒性休克的一系列事件。尽管存在高水平的循环内毒素，但这种保护作用仍然发生了。
