In vivo cytokine response to Escherichia coli alpha-hemolysin determined with genetically engineered hemolytic and nonhemolytic E. coli variants.
In vivo cytokine response to Escherichia coli alpha-hemolysin determined with genetically engineered hemolytic and nonhemolytic E. coli variants.
复制标题
使用基因工程溶血和非溶血大肠杆菌变体测定体内细胞因子对大肠杆菌α-溶血素的反应。
DOI：
10.1128/iai.64.6.2167-2171.1996
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发表时间：
1996
影响因子：
3.1
通讯作者：
Pruett,TL
中科院分区：
文献类型：
--
作者：
May,AK;Sawyer,RG;Gleason,T;Whitworth,A;Pruett,TL
α-溶血素是一种增强细菌毒力的大肠杆菌外毒素，在体外对白细胞有深刻的作用，在体外能诱导人单核细胞释放白细胞介素1(IL-1)，但不能诱导肿瘤坏死因子(TNF)的释放。本研究的目的是检测α-溶血素对病毒毒力以及体内产生肿瘤坏死因子和白介素1的影响。使用了两个基因工程的同源大肠杆菌菌株；一个变种产生α-溶血素，另一个变种不产生。给雄性BALB/c小鼠注射这两种变异体中的任何一种，检测血清中肿瘤坏死因子和白介素1的水平。将这些结果与注射两种血清型脂多糖(LPS)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，血清中的肿瘤坏死因子或白介素1水平也没有显著升高。相反，等量接种溶血性大肠杆菌菌株可显著提高死亡率和血清IL-1水平。尽管死亡率较高，但在这组患者中未发现肿瘤坏死因子水平显著升高。一种诱导死亡率和血清IL-1水平升高而没有血清肿瘤坏死因子水平升高的模式与典型的内毒素模式不同。在这些实验中，无论是否导致死亡，两种血清型的内毒素都会导致肿瘤坏死因子和白介素1水平的升高。因此，α-溶血素在体内产生的细胞因子反应与Bhakdi等人先前在体外证明的类似。(S.Bhakdi，M.Muhly，S.Korom和G.Schmidt，J.Clin.投资。85：1746-1753,1990)，并且似乎独立于血清肿瘤坏死因子而导致死亡。
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.