Immunotherapeutic modification of Escherichia coli--induced experimental peritonitis and bacteremia by glucan.
Immunotherapeutic modification of Escherichia coli--induced experimental peritonitis and bacteremia by glucan.
复制标题
葡聚糖对大肠杆菌诱导的实验性腹膜炎和菌血症的免疫治疗修饰。
作者：
D. Williams;I. Browder;N. di Luzio
我们实验室以前的数据表明，葡聚糖的施用显著改变了多种实验诱导的传染病的病程。鉴于革兰氏阴性感染的发病率越来越高，我们开始研究腹腔内葡聚糖治疗对大肠杆菌引起的腹膜炎和败血症的影响。雄性ICR/Tex小鼠在腹腔注射1.0 × 10(8)大肠杆菌前的第5天和第3天腹腔注射葡聚糖或葡萄糖。给予葡聚糖可显著提高生存率。对葡聚糖保护作用机制的评估显示，葡聚糖组和葡萄糖对照组在早期均显示出相当水平的血源性大肠杆菌。攻击后6小时，葡聚糖组血源性大肠杆菌显著减少。相反，葡萄糖对照组表现为进行性菌血症。与未暴露于细菌攻击的对照组小鼠相比，大肠杆菌感染小鼠的吞噬活性明显下降。在对照组中观察到的葡聚糖处理小鼠的吞噬功能增强在大肠杆菌攻击和葡聚糖处理小鼠中没有改变。高功能巨噬细胞在降低大肠杆菌脓毒症死亡率中的可能重要性通过棕榈酸甲酯诱导葡聚糖高功能状态的逆转来表示。棕榈酸甲酯处理的葡聚糖注射小鼠对大肠杆菌感染没有保护作用。这些数据表明，腹腔注射葡聚糖可以显著改变大肠杆菌诱导的腹膜炎和菌血症的病程，部分原因是葡聚糖诱导的巨噬细胞功能增强。
Previous data from our laboratory have demonstrated that glucan administration significantly alters the course of a variety of experimentally induced infectious diseases. In view of the increasing incidence of gram-negative infections, studies were initiated to evaluate the effect of intraperitoneal glucan therapy on Escherichia coli-induced peritonitis and sepsis. Male ICR/Tex mice were injected intraperitoneally with glucan or dextrose on days 5 and 3 prior to intraperitoneal challenge with 1.0 x 10(8) E. coli. Glucan administration resulted in a significant enhancement of survival. Evaluation of the mechanism of protective action of glucan revealed that both the glucan and dextrose control groups showed an equivalent level of blood-borne E. coli at early periods. At 6 hours after challenge the glucan group showed a significant decrease in blood-borne E. coli. In contrast, the dextrose control group demonstrated progressive bacteremia. A significant depression of phagocytic activity occurred in E. coli-infected mice as compared with control mice that were not exposed to the bacterial challenge. The enhancement in phagocytic function observed in glucan-treated control mice was unaltered in E. coli challenged, glucan-treated mice. The possible importance of hyperfunctional macrophages in reduction of mortality from E. coli sepsis was denoted by methyl palmitate-induced reversal of the glucan hyperfunctional state. Methyl palmitate-treated glucan injected mice were not protected against E. coli infection. These data denote that the intraperitoneal administration of glucan significantly modifies the course of E. coli-induced peritonitis and bacteremia due, in part, to glucan-induced enhancement of macrophage function.