首页> 外文期刊>Infection and immunity >Enhanced protection by use of a combination of anticapsule and antilipopolysaccharide monoclonal antibodies against lethal Escherichia coli O18K5 infection of mice.
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Enhanced protection by use of a combination of anticapsule and antilipopolysaccharide monoclonal antibodies against lethal Escherichia coli O18K5 infection of mice.

机译:通过使用抗胶囊和抗脂多糖单克隆抗体的组合来增强对小鼠致死性大肠杆菌O18K5感染的保护。

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To study antibody-mediated protection against Escherichia coli peritonitis in BALB/c mice, monoclonal antibodies (MAbs) were generated against the capsule (K5) and the lipopolysaccharide (O18) of E. coli. Flow cytometric analysis with two selected immunoglobulin M MAbs revealed that bacteria were antigenically heterogeneous. Arbitrarily, three subpopulations in E. coli O18K5 cultures could be distinguished by double immunofluorescence. A subpopulation bound only the anti-K5 MAb, and another subpopulation bound only the anti-O18 MAb. An intermediate subpopulation, however, bound both MAbs. In agreement with this result, combinations of both MAbs enhanced phagocytosis of fluorescein isothiocyanate-labeled bacteria by human polymorphonuclear leukocytes and mouse macrophage J774 cells as well. In protection experiments, combinations of both MAbs, preincubated with 3 50% lethal doses of E. coli O18K5, protected all mice upon intraperitoneal challenge. Relatively high doses of either MAb alone proved to be not fully protective in this infection model. Protection of mice by the combination of MAbs was associated with significantly lower (P < 0.02) tumor necrosis factor levels in serum 90 min after challenge compared with any other treatment group. Similarly, prophylactic administration of MAbs yielded significantly lower (P < 0.01) tumor necrosis factor levels in mice that received the combination of MAbs than in any other treatment group.
机译:为了研究BALB / c小鼠中抗体介导的抗大肠杆菌腹膜炎的保护作用,产生了针对大肠杆菌的胶囊(K5)和脂多糖(O18)的单克隆抗体(MAb)。用两个选定的免疫球蛋白M MAb进行的流式细胞仪分析表明细菌是抗原异质的。任意地,大肠杆菌O18K5培养物中的三个亚群可以通过双重免疫荧光来区分。一个亚群仅结合抗-K5 MAb,另一个亚群仅结合抗-O18 MAb。然而,中间亚群结合了两个MAb。与该结果一致,两种MAb的组合也增强了人多形核白细胞和小鼠巨噬细胞J774细胞对异硫氰酸荧光素标记的细菌的吞噬作用。在保护实验中,将两种MAb的组合与3个50%致死剂量的大肠杆菌O18K5预孵育,可在腹膜内攻击时保护所有小鼠。在这种感染模型中,单独使用相对高剂量的两种单克隆抗体均不能完全起到保护作用。与其他治疗组相比,攻击后90分钟血清中单克隆抗体的结合对小鼠的肿瘤坏死因子水平显着降低(P <0.02)。同样,与其他治疗组相比,预防性给予MAb的小鼠产生的肿瘤坏死因子水平显着降低(P <0.01)。

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