超抗原SEA对人胃癌细胞株小鼠荷瘤模型作用及其机制的研究

目的　探讨超抗原金黄色葡萄球菌肠毒素 (SEA)对体内肿瘤的抑瘤效果及作用机制。方法　采用人胃癌细胞 (MGC80 3 )皮下接种建立小鼠胃癌模型 (n =40 ) ,实验组 (n =2 0 )注射SEA ,对照组 (n =2 0 )注射生理盐水 ,观察肿瘤的发生率及肿瘤的重量。并对瘤体组织应用免疫组织化学方法初步探讨其发生机制。结果　超抗原SEA处理的小鼠肿瘤的发生率低于对照组 ,两者差异无显著性 ;超抗原SEA处理的小鼠肿瘤的重量明显低于对照组 ,两者差异有显著性 (P <0 .0 1) ;SEA处理的小鼠肿瘤组织有CD4 T细胞和CD8 T细胞浸润 ,而对照组很少或没有T细胞浸润。结论　超抗原SEA对小鼠胃癌细胞有明显抑瘤效果 ,其作用机制可能为SEA诱导了超抗原依赖细胞介导的细胞毒效应所致     

Staphylococcal superantigens and toxins are detectable in the serum of adult burn patients

Bacterial infection in burn patients is still a devastating contributor to morbidity and mortality. Little is known regarding the presence of staphylococcal toxins in the burn-injured patient. The aim of this study was to characterize the prevalence of several of these toxins and their relationship to clinical metrics and mortality in burn patients. Levels of exotoxins staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B, toxic shock syndrome toxin 1 (TSST-1), and α-hemolysin were assayed from the serum of 207 adult burn patients aged 16–92 years. Clinical, demographic, and microbiological data from these patients were then compared to toxin levels. Staphylococcal exotoxins α-hemolysin and SEA were present in 45% and 25% of the population, respectively. Bacterial cultures concomitantly showed a high prevalence of Staphylococcus aureus in 48% of patients, of which 59% were methicillin resistant. Several metrics may be predictive of high toxin concentrations of α-hemolysin and TSST-1 and SEA including burn size, length of stay, and bacteremia. Mortality associations indicated that burn size, bacteremia, age, and the presence of α-hemolysin and SEA may be predictors of mortality. A high prevalence of staphylococcal toxin α-hemolysin and superantigens TSST-1 and SEA can be found in the circulation of the adult burn population. The presence of these toxins may contribute to the morbidity and mortality of the burn patient.     

Evaluation of anti-Yersinia psueudotuberculosis-derived mitogen antibody in intravenous immunoglobulin products

Antibody titers against the superantigen, Yersinia pseudotuberculosis-derived mitogen, suggestive of mediating Kawasaki disease-like manifestation in Y. pseudotuberculosis infections, in immunoglobulin products were evaluated. Trace, but detectable titer was demonstrated in the products. Thus, attention is required when evaluating anti-Y. pseudotuberculosis-derived mitogen IgG titers in patient sera post intravenous immunoglobulin therapy.     

Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST-1

The pathogenesis of the toxic shock syndrome (TSS) is only incompletely understood. We now present evidence that TSS toxin-1 (TSST-1), one of the superantigens produced by Staphylococcus aureus, induces lethal shock in D-galactosamine sensitized mice. In this model TSS is dependent on T cells, since cyclosporin A (CsA) completely blocked development of shock, and since T cell-deficient SCID mice did not show signs of disease upon injection with TSST-1. However, SCID mice repopulated with T cells succumbed to lethal shock. The disease is characterized by a burst of lymphokines like interleukin-2 (IL-2) and tumor necrosis factor (TNF) released into the sera of TSST-1-treated animals. Already 1–2 h after TSST-1 application TNF serum levels peaked and IL-2 levels peaked around 4 h after treatment. TNF appears as key mediator of TSS, because anti-TNF monoclonal antibodies protected TSST-1-challenged mice. Interestingly, the burst of TNF in serum was noted well in advance of detectable markers of T cell activation. Thus, about 5 % of all peripheral T cells started to express the IL-2 receptors as late as 4 h after treatment. Comparing TSST-1- and endotoxin-induced shock we conclude that TNF effects shock in both diseases. However, the type of cells involved appears distinct in that T cells cause TSS triggered by the exotosin TSST-1 while macrophages mediate the shock induced by endotoxins.     

携带超抗原SEA基因的白蛋白纳米载体的构建及其治疗膀胱癌潜能研究

目的 构建一种非病毒载体基因投递系统-携带超抗原葡萄球菌肠毒素A(SEA)基因的白蛋白纳米载体,观察白蛋白纳米粒表征并探讨其潜在的靶向基因投递作用和强大的抗瘤机制.方法 采用去溶剂化法制备白蛋白纳米粒,平均粒径(253.1±11.9)nm,Zeta电位(-34.0±4.5)mV,PDI 0.43±0.04;抽提SEA基因质粒(pSEA)260/280:1.84±0.02,pSEA浓度:(85.54±1.43)mg/L;经生物活性及基因测序鉴定后耦合SEA基因质粒和白蛋白纳米载体,并观察耦合物的稳定性及白蛋白纳米载体对SEA基因的保护作用.结果 成功构建携带超抗原SFA基因的白蛋白纳米载体,平均粒径(118.9±4.8)nm,Zeta电位(-43.9±10.5)mV,PDI 0.19±0.02,基因转载率为(97.61±0.06)%,性质稳定、分散性较好,体外实验表明白蛋白纳米载体能保护SEA基因免受DNase Ⅰ的降解.结论 获得符合超抗原SEA基因转染要求的白蛋白纳米载体.

Abstract：

Objective To assess the characteristics of human serum albumin nanoparticles (HSA-NP) as a nonviral vector system for delivery staphylococcal enterotoxin A (SEA) gene and probe into its potential targeted antitumor mechanism.Methods HSA-NP and plasmid containing SEA gene (pSEA)encapsulated in HSA (pSEA-HSA-NP) were prepared by a desolvation-crosslinking method.HSA-NP had a mean size of (253.1 ± 11.9) nm,zeta potential of ( -34.0 ±4.5) mV,polydispersity index of 0.43 ±0.04.The superantigen SEA gene was extracted by the Endo-Free Plasmid Maxi Kit,260/280 of pSEA was 1.84 ±0.02 and the concentration of pSEA was ( 85.54 ± 1.43 ) mg/L.pSEA was verified by sequencing and biological activity survey,the stability of pSEA-HSA-NP was investigated by laying for 10 days at room temperature,and the size and zeta potential were remeasured and contrasted with the samples 10 days before.HSA-NP protecting pSEA from degradation of DNase I was detected by gel electrophoresis.Results Electrophoretic mobility analysis and fluorescent labeling revealed that pSEA-HSA-NP was successfully constructed.PSEA-HSA-NP had a mean size of ( 118.9 ±4.8) nm,zeta potential of ( -43.9 ± 10.5 ) mV,polydispersity index of 0.19 ±0.02 and pSEA encapsulation efficiency of (97.61 ±0.06)%.The characteristics of pSEA-HSA-NP solution laying for 10 days at room temperature indicated a better stability and polydispersity.HSA-NP stabilizing pSEA against DNase I in vitro was also testified by gel electrophoresis.Conclusion pPSEA-HSA-NP served the transfecting needs of superantigen SEA gene.     

金黄色葡萄球菌肠毒素与慢性鼻-鼻窦炎 相关性的研究进展

近年来国际上针对慢性鼻-鼻窦炎病因学提出“超抗原”学说,金黄色葡萄球菌分泌的肠毒素作为一种外源性超抗原,仅需微量即可刺激多种非特异性T细胞大量增殖,产生多种细胞因子,在疾病的发生发展过程中发挥重要作用。本文将对金黄色葡萄球菌肠毒素的结构、作用机理及与慢性鼻-鼻窦炎相关研究进行综述。