Rosen H, Orman J, Rakita R M, Michel B R, VanDevanter D R
Department of Medicine, University of Washington, Seattle.
Proc Natl Acad Sci U S A. 1990 Dec;87(24):10048-52. doi: 10.1073/pnas.87.24.10048.
Neutrophils and monocytes employ a diverse array of antimicrobial effector systems to support their host defense functions. The mechanisms of action of most of these systems are incompletely understood. The present report indicates that microbicidal activity by a neutrophil-derived antimicrobial system, consisting of myeloperoxidase, enzymatically generated hydrogen peroxide, and chloride ion, is accompanied by prompt cessation of DNA synthesis in Escherichia coli, as determined by markedly reduced incorporation of [3H]thymidine into trichloracetic acid-precipitable material. Simultaneously, the myeloperoxidase system mediates a decline in the ability of E. coli membranes to bind hemimethylated DNA sequences containing the E. coli chromosomal origin of replication (oriC). Binding of oriC to the E. coli membrane is an essential element of orderly chromosomal DNA replication. Comparable early changes in DNA synthesis and DNA-membrane interactions were not observed with alternative oxidant or antibiotic-mediated microbicidal systems. It is proposed that oxidants generated by the myeloperoxidase system modify the E. coli membrane in such a fashion that oriC binding is markedly impaired. As a consequence chromosomal DNA replication is impaired and organisms can no longer replicate.
中性粒细胞和单核细胞利用多种抗菌效应系统来支持其宿主防御功能。这些系统中大多数的作用机制尚未完全了解。本报告指出，由髓过氧化物酶、酶促产生的过氧化氢和氯离子组成的中性粒细胞衍生抗菌系统的杀菌活性，伴随着大肠杆菌DNA合成的迅速停止，这是通过[3H]胸苷掺入三氯乙酸可沉淀物质的显著减少来确定的。同时，髓过氧化物酶系统介导大肠杆菌膜结合含有大肠杆菌染色体复制起点（oriC）的半甲基化DNA序列的能力下降。oriC与大肠杆菌膜的结合是有序染色体DNA复制的一个基本要素。在替代氧化剂或抗生素介导的杀菌系统中未观察到DNA合成和DNA-膜相互作用的类似早期变化。有人提出，髓过氧化物酶系统产生的氧化剂以一种显著损害oriC结合的方式修饰大肠杆菌膜。因此，染色体DNA复制受损，生物体无法再进行复制。
