Miedzybrodzki Ryszard, Switala-Jelen Kinga, Fortuna Wojciech, Weber-Dabrowska Beata, Przerwa Anna, Lusiak-Szelachowska Marzanna, Dabrowska Krystyna, Kurzepa Aneta, Boratynski Janusz, Syper Danuta, Pozniak Gryzelda, Lugowski Czeslaw, Gorski Andrzej
Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland.
Virus Res. 2008 Feb;131(2):233-42. doi: 10.1016/j.virusres.2007.09.013. Epub 2007 Nov 9.
It has been known that administration of antibiotics may lead to excessive release of bacterial endotoxins and complicate clinical course of patients with Gram-negative infections. This concern may also apply to phages. Endotoxin may in turn activate neutrophils to produce reactive oxygen species (ROS) that are believed to play an important role in the pathogenesis of multiple organ dysfunction in the course of sepsis. We showed that a purified T4 phage preparation with low-endotoxin content could significantly diminish the luminol-dependent chemiluminescence (CL) of peripheral blood polymorphonuclear leukocytes (PMNs) both stimulated by lipopolysaccharides (LPSs) isolated from different Escherichia coli strains. This effect was also observed for live bacteria used for PMNs stimulation and was independent of bacterial susceptibility for T4-mediated lysis. Our data suggest, that phage-mediated inhibition of LPS- or bacteria-stimulated ROS production by PMNs may be attributed not only to phage-PMNs interactions, but also to phage-LPS interactions and bacterial lysis (in case of homologous phage). Interestingly, the T4 preparation did not influence ROS formation by PMNs stimulated with PMA. This suggests that the observed phenomena are also dependent upon the nature of activator. Bacteriophage-mediated inhibition of ROS formation by cells exposed to endotoxin provides new evidence for possible interactions between phages and mammalian cells. It helps in understanding the role of phages in our environment and may also be of important clinical significance.
已知使用抗生素可能导致细菌内毒素过度释放，并使革兰氏阴性菌感染患者的临床病程复杂化。这种担忧可能也适用于噬菌体。内毒素进而可能激活中性粒细胞产生活性氧（ROS），据信活性氧在脓毒症过程中多器官功能障碍的发病机制中起重要作用。我们发现，一种内毒素含量低的纯化T4噬菌体制剂能够显著降低由从不同大肠杆菌菌株分离的脂多糖（LPS）刺激的外周血多形核白细胞（PMN）的鲁米诺依赖性化学发光（CL）。在用活细菌刺激PMN时也观察到了这种效果，并且该效果与细菌对T4介导裂解的敏感性无关。我们的数据表明，噬菌体介导的PMN对LPS或细菌刺激的ROS产生的抑制作用可能不仅归因于噬菌体与PMN的相互作用，还归因于噬菌体与LPS的相互作用以及细菌裂解（在同源噬菌体的情况下）。有趣的是，T4制剂不影响由佛波酯（PMA）刺激的PMN产生ROS。这表明观察到的现象也取决于激活剂的性质。噬菌体介导的对暴露于内毒素的细胞ROS形成的抑制作用为噬菌体与哺乳动物细胞之间可能的相互作用提供了新证据。这有助于理解噬菌体在我们环境中的作用，也可能具有重要的临床意义。
