首页> 外文期刊>Infection and immunity >In vivo cytokine response to Escherichia coli alpha-hemolysin determined with genetically engineered hemolytic and nonhemolytic E. coli variants.
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In vivo cytokine response to Escherichia coli alpha-hemolysin determined with genetically engineered hemolytic and nonhemolytic E. coli variants.

机译:用基因工程溶血和非溶血大肠杆菌变异体确定的对大肠杆菌α-溶血素的体内细胞因子反应。

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Alpha-hemolysin is an Escherichia coli exotoxin that enhances bacterial virulence, has profound effects on leukocytes in vitro, and induces the release of interleukin-1 (IL-1) but not tumor necrosis factor (TNF) from human monocytes in vitro. The purpose of this study was to examine alpha-hemolysin's influence on virulence and TNF and IL-1 production in vivo. Two genetically engineered, isogeneic strains of E. coli were used; one variant produces alpha-hemolysin, and the other does not. Male BALB/c mice were injected with either of the two variants and serum TNF and IL-1 were assayed. These results were compared with those obtained from the injection of either of two serotypes of lipopolysaccharide (LPS). The nonhemolytic E. coli strain produced no mortality and no significant elevation of serum TNF or IL-1 levels. In contrast, equal inocula of the hemolytic E. coli strain produced significant mortality and elevation of serum IL-1 levels. No significant elevation of TNF levels was detected in this group despite high-level mortality. A pattern of induction of mortality and elevation of serum IL-1 levels without elevation of serum TNF levels is distinct from the pattern typical of LPS. In these experiments, both serotypes of LPS caused elevations of TNF and IL-1 levels whether or not mortality was induced. Thus, alpha-hemolysin produces a cytokine response in vivo that is similar to that previously demonstrated in vitro by Bhakdi et al. (S. Bhakdi, M. Muhly, S. Korom, and G. Schmidt, J. Clin. Invest. 85:1746-1753, 1990) and appears to induce mortality independently of serum TNF.
机译:α-溶血素是一种大肠杆菌外毒素,可增强细菌毒性,对体外白细胞具有深远的影响,并在体外诱导人单核细胞释放白介素-1(IL-1)而不诱导肿瘤坏死因子(TNF)释放。这项研究的目的是检查α-溶血素对体内毒力以及TNF和IL-1产生的影响。使用了两种基因工程的大肠杆菌同基因菌株。一种变体产生α-溶血素,而另一种不产生。给雄性BALB / c小鼠注射两种变体中的任一种,并测定血清TNF和IL-1。将这些结果与注射两种血清型脂多糖(LPS)所得的结果进行了比较。非溶血性大肠杆菌菌株没有产生死亡率,血清TNF或IL-1水平也没有明显升高。相反,溶血性大肠杆菌菌株的相同接种量会产生明显的死亡率并升高血清IL-1水平。尽管死亡率高,但该组中未检测到TNF水平的显着升高。死亡率的诱导和血清IL-1水平升高而不血清TNF水平升高的模式与LPS的典型模式不同。在这些实验中,无论是否诱发死亡率,LPS的两种血清型均引起TNF和IL-1水平的升高。因此,α-溶血素在体内产生细胞因子应答,类似于先前由Bhakdi等人在体外所证实的。 (S.Bhakdi,M.Muhly,S.Korom和G.Schmidt,J.Clin.Invest.85:1746-1753,1990),并且似乎可以独立于血清TNF诱导死亡率。

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