Redundant contribution of myeloperoxidase-dependent systems to neutrophil-mediated killing of Escherichia coli.
Redundant contribution of myeloperoxidase-dependent systems to neutrophil-mediated killing of Escherichia coli.
复制标题
髓过氧化物酶依赖性系统对中性粒细胞介导的大肠杆菌杀伤的冗余贡献。
DOI：
10.1128/iai.65.10.4173-4178.1997
复制
发表时间：
1997
影响因子：
3.1
通讯作者：
Michel,BR
中科院分区：
文献类型：
--
作者：
Rosen,H;Michel,BR
中性粒细胞杀微生物活性是重叠的抗微生物系统的结果，其根据微生物-微生物相互作用的条件、微生物的性质及其代谢状态而显著变化。在这项研究中，正常、髓过氧化物酶缺乏和呼吸爆发缺乏（慢性肉芽肿病[CGD]）的中性粒细胞以同等的高效率杀死大肠杆菌。杀CGD和髓过氧化物酶缺陷的中性粒细胞没有增加补充剂，如外源性H2O2和髓过氧化物酶，旨在改善他们的代谢缺陷，这表明非氧化性杀微生物系统是足够的一个完整的杀微生物效果。具有完整髓过氧化物酶抗菌系统的中性粒细胞（正常或适当补充的缺陷细胞）能够快速抑制E。大肠杆菌DNA合成，而未补充CGD或髓过氧化物酶缺陷细胞的效果要差得多，这表明髓过氧化物酶系统在正常中性粒细胞中是活跃的。在无细胞系统中，髓过氧化物酶充足的中性粒细胞对DNA合成的抑制程度可以解释观察到的大部分杀微生物活性。虽然髓过氧化物酶系统是活跃的，可能是杀菌的，但它不是杀菌活性的速率限制，并且似乎与细胞中的其他杀菌系统是多余的。细菌DNA合成的快速和广泛抑制似乎是中性粒细胞中髓过氧化物酶活性的指标。
Neutrophil microbicidal activity is a consequence of overlapping antimicrobial systems that vary in prominence according to the conditions of the neutrophil-microbe interaction, the nature of the microbe, and its metabolic state. In this study, normal, myeloperoxidase-deficient, and respiratory burst-deficient (chronic granulomatous disease [CGD]) neutrophils killed Escherichia coli with equivalent, high efficiencies. Killing by CGD and myeloperoxidase-deficient neutrophils was not augmented by supplements, such as exogenous H2O2 and myeloperoxidase, directed at ameliorating their metabolic defects, suggesting that nonoxidative microbicidal systems were sufficient for a full microbicidal effect. Neutrophils with an intact myeloperoxidase antimicrobial system (normal or appropriately supplemented deficient cells) were capable of rapidly suppressing E. coli DNA synthesis, while unsupplemented CGD or myeloperoxidase-deficient cells were far less effective, indicating that the myeloperoxidase system was active in normal neutrophils. The degree of DNA synthesis inhibition by myeloperoxidase-sufficient neutrophils could account, in a cell-free system, for most of the observed microbicidal activity. While the myeloperoxidase system was active and probably bactericidal, it was not rate limiting for microbicidal activity and appears to have been redundant with other microbicidal systems in the cell. Rapid and extensive inhibition of bacterial DNA synthesis appears to be an indicator of myeloperoxidase activity in neutrophils.