Murray H W, Juangbhanich C W, Nathan C F, Cohn Z A
J Exp Med. 1979 Oct 1;150(4):950-64. doi: 10.1084/jem.150.4.950.
The capacity of three populations of mouse peritoneal macrophages to generate oxidative metabolites (as judged by extracellular release of H2O2) was compared to their ability to influence the intracellular fate of virulent Toxoplasma gondii. Macrophages from normal mice released little H2O2 and allowed unrestricted multiplication of intracellular toxoplasmas. Cells from chronically infected, immune (IM) mice released 4 times more H2O2 and displayed microbistatic activity. In contrast, macrophages from immune-boosted (IB) mice released 25 times more H2O2 than normal cells and rapidly killed the bulk of ingested toxoplasmas within 1 h. When macrophage monolayers were exposed to scavengers of O2-, H2O2, OH., and 1O2, both the inhibition of intracellular toxoplasma multiplication by IM macrophages and the killing of toxoplasmas by IB macrophages were reversed. Depriving cells of glucose, which markedly reduced H2O2 release, resulted in similar reversal of IM and IB macrophage anti-toxoplasma activity. As judged by the effect of the individual oxygen intermediate scavengers, O2- and H2O2 appeared to serve as precursors for the key toxic agents which may include OH. and 1O2. Providing normal macrophages with an exogenous source of oxidative metabolites generated by xanthine and xanthine oxidase, but not glucose and glucose oxidase, resulted in inhibition of intracellular toxoplasma growth. These findings suggest the presence of an oxygen-dependent antimicrobial system in mononuclear phagocytes beyond the production of O2- and H2O2, and indicate an important role for oxygen intermediates in macrophage resistance to the intracellular pathogen T. gondii.
比较了三组小鼠腹腔巨噬细胞产生氧化代谢产物的能力（通过细胞外释放H2O2来判断）及其影响强毒力弓形虫细胞内命运的能力。正常小鼠的巨噬细胞释放少量H2O2，并允许细胞内弓形虫不受限制地繁殖。慢性感染的免疫（IM）小鼠的细胞释放的H2O2多4倍，并表现出抑菌活性。相比之下，免疫增强（IB）小鼠的巨噬细胞释放的H2O2比正常细胞多25倍，并在1小时内迅速杀死大部分摄入的弓形虫。当巨噬细胞单层暴露于O2-、H2O2、OH.和1O2的清除剂时，IM巨噬细胞对细胞内弓形虫繁殖的抑制作用以及IB巨噬细胞对弓形虫的杀伤作用均被逆转。剥夺细胞葡萄糖会显著减少H2O2的释放，导致IM和IB巨噬细胞抗弓形虫活性出现类似的逆转。根据单个氧中间产物清除剂的作用判断，O2-和H2O2似乎是关键毒性因子的前体，这些毒性因子可能包括OH.和1O2。为正常巨噬细胞提供由黄嘌呤和黄嘌呤氧化酶产生的氧化代谢产物的外源来源，但不是葡萄糖和葡萄糖氧化酶，会导致细胞内弓形虫生长受到抑制。这些发现表明单核吞噬细胞中存在一种依赖氧的抗菌系统，其作用超出了O2-和H2O2的产生，并表明氧中间产物在巨噬细胞抵抗细胞内病原体弓形虫中起重要作用。
