Víctor Víctor Manuel, Rocha Milagros, De la Fuente Mónica
Department of Animal Physiology, Faculty of Biological Sciences, Complutense University, 28040 Madrid, Spain.
Int Immunopharmacol. 2003 Jan;3(1):97-106. doi: 10.1016/s1567-5769(02)00232-1.
Changes in several functions of peritoneal macrophages from mice with oxidative stress caused by intraperitoneal injection of endotoxin (Escherichia coli lipopolysaccharide, LPS) (100 mg/kg), and associated with a high production of reactive oxygen species (ROS), have been observed in our previous studies. Antioxidants such as N-acetylcysteine (NAC) are free radical scavengers that improve and modulate the immune response, especially in oxidative stress situations. Therefore, in the present work, we have studied the effects of the administration of NAC (150 mg/kg i.p.) on different functions of peritoneal macrophages from Swiss mice suffering that oxidative stress, caused by LPS (100 mg/kg). NAC was injected 30 min after LPS injection, and the peritoneal macrophages were obtained at 2, 4, 12, and 24 h after endotoxin injection. The following functions, key stages of the phagocytic process, were studied: adherence to substrate, chemotaxis, ingestion of particles, and production of ROS (reactive oxygen species), as well as tumor necrosis factor (TNFalpha) release. The decrease in chemotaxis and the increase in adherence, ingestion, superoxide anion production, and TNFalpha release shown by macrophages from animals with oxidative stress were counteracted by NAC injection. These data suggest that NAC administration may be useful for the treatment of oxidative stress-linked endotoxic shock, modulating the function of macrophages, specifically in decreasing the production of ROS and of inflammatory cytokines such as TNFalpha.
在我们之前的研究中，观察到腹腔注射内毒素（大肠杆菌脂多糖，LPS）（100mg/kg）导致氧化应激的小鼠腹膜巨噬细胞的几种功能发生变化，且与活性氧（ROS）的高产生有关。抗氧化剂如N-乙酰半胱氨酸（NAC）是自由基清除剂，可改善和调节免疫反应，尤其是在氧化应激情况下。因此，在本研究中，我们研究了给予NAC（150mg/kg腹腔注射）对遭受LPS（100mg/kg）引起的氧化应激的瑞士小鼠腹膜巨噬细胞不同功能的影响。在LPS注射后30分钟注射NAC，并在内毒素注射后2、4、12和24小时获取腹膜巨噬细胞。研究了吞噬过程关键阶段的以下功能：对底物的粘附、趋化性、颗粒摄取、ROS（活性氧）产生以及肿瘤坏死因子（TNFα）释放。氧化应激动物的巨噬细胞显示的趋化性降低以及粘附、摄取、超氧阴离子产生和TNFα释放增加，通过注射NAC得以抵消。这些数据表明，给予NAC可能有助于治疗与氧化应激相关的内毒素休克，调节巨噬细胞的功能，特别是减少ROS和炎性细胞因子如TNFα的产生。
