May James M, Li Liying, Qu Zhi-Chao, Huang Junjun
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6303, USA.
Arch Biochem Biophys. 2005 Aug 15;440(2):165-72. doi: 10.1016/j.abb.2005.06.018.
Since activated macrophages generate potentially deleterious reactive oxygen species, we studied whether ascorbic acid might function as an antioxidant in these cells. Thioglycollate-elicited murine peritoneal macrophages contained about 3 mM ascorbate that was halved by culture in ascorbate-free medium. However, the cells took up added ascorbate to concentrations of 6-8 mM by a high-affinity sodium-dependent transport mechanism. This likely reflected the activity of the SVCT2 ascorbate transporter, since its message and protein were present in the cells. Activation of the cells by phagocytosis of latex particles depleted intracellular ascorbate, although not below the basal levels present in the cells in culture. Glutathione (GSH) was unaffected by phagocytosis, suggesting that ascorbate was more sensitive to the oxidant stress of phagocytosis than GSH. Phagocytosis induced a modest increase in reactive oxygen species as well as a progressive loss of alpha-tocopherol, both of which were prevented in cells loaded with ascorbate. These results suggest that activated macrophages can use ascorbate to lessen self-generated oxidant stress and spare alpha-tocopherol, which may protect these long-lived cells from necrosis or apoptosis.
由于活化的巨噬细胞会产生潜在有害的活性氧，我们研究了抗坏血酸在这些细胞中是否可能作为一种抗氧化剂发挥作用。巯基乙酸盐诱导的小鼠腹腔巨噬细胞含有约3 mM的抗坏血酸，在无抗坏血酸的培养基中培养后其含量减半。然而，细胞通过一种高亲和力的钠依赖性转运机制摄取添加的抗坏血酸，使其浓度达到6 - 8 mM。这可能反映了SVCT2抗坏血酸转运体的活性，因为细胞中存在其信使核糖核酸和蛋白质。通过吞噬乳胶颗粒激活细胞会消耗细胞内的抗坏血酸，尽管不会低于培养细胞中的基础水平。谷胱甘肽（GSH）不受吞噬作用的影响，这表明抗坏血酸比GSH对吞噬作用的氧化应激更敏感。吞噬作用会导致活性氧适度增加以及α - 生育酚逐渐损失，而在加载了抗坏血酸的细胞中这两种情况都得到了预防。这些结果表明，活化的巨噬细胞可以利用抗坏血酸来减轻自身产生的氧化应激并节省α - 生育酚，这可能保护这些长寿细胞免于坏死或凋亡。
