Arthur M J, Kowalski-Saunders P, Wright R
Department of Medicine II, Southampton General Hospital, United Kingdom.
Gastroenterology. 1988 Dec;95(6):1588-94. doi: 10.1016/s0016-5085(88)80082-9.
Reactive oxygen intermediates released by activated hepatic macrophages have been implicated in the pathogenesis of a rat model of liver injury induced by sequential administration of Corynebacterium parvum and endotoxin. In this model, C. parvum causes extensive infiltration of the liver with activated macrophages, but severe liver injury occurs only after subsequent exposure to endotoxin. We have therefore investigated the effects of endotoxin on the release of reactive oxygen intermediates by C. parvum-activated hepatic macrophages. After in vitro exposure to zymosan, opsonized zymosan, or phorbol myristate acetate, hepatic macrophages isolated from C. parvum- and endotoxin-treated rats demonstrated significantly (1.5-2-fold) increased release of superoxide and oxidation of [1-14C]glucose via the hexose monophosphate shunt compared with hepatic macrophages isolated from C. parvum- and saline-treated control rats. These results indicate that endotoxin enhances the state of activation of hepatic macrophages already partially activated by C. parvum. We suggest that the increased release of reactive oxygen intermediates by these cells promotes liver injury in this model.
活化的肝巨噬细胞释放的活性氧中间体与通过先后给予短小棒状杆菌和内毒素诱导的大鼠肝损伤模型的发病机制有关。在这个模型中，短小棒状杆菌会导致肝内被活化的巨噬细胞大量浸润，但严重的肝损伤仅在随后接触内毒素后才会发生。因此，我们研究了内毒素对短小棒状杆菌活化的肝巨噬细胞释放活性氧中间体的影响。在体外暴露于酵母聚糖、调理酵母聚糖或佛波酯肉豆蔻酸酯后，从经短小棒状杆菌和内毒素处理的大鼠分离的肝巨噬细胞与从经短小棒状杆菌和生理盐水处理的对照大鼠分离的肝巨噬细胞相比，超氧化物的释放显著增加（1.5至2倍），并且通过磷酸己糖途径使[1-14C]葡萄糖氧化增加。这些结果表明，内毒素增强了已被短小棒状杆菌部分活化的肝巨噬细胞的活化状态。我们认为，这些细胞释放的活性氧中间体增加促进了该模型中的肝损伤。
