title: Bacteriophage preparation inhibition of reactive oxygen species generation by endotoxin-stimulated polymorphonuclear leukocytes.
abstract: 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.
authors.affiliation: Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland. mbrodzki@iitd.pan.wroc.pl
authors.forename: Ryszard
authors.initials: R
authors.lastname: Miedzybrodzki
authors.forename: Kinga
authors.initials: K
authors.lastname: Switala-Jelen
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fortuna
authors.forename: Beata
authors.initials: B
authors.lastname: Weber-Dabrowska
authors.forename: Anna
authors.initials: A
authors.lastname: Przerwa
authors.forename: Marzanna
authors.initials: M
authors.lastname: Lusiak-Szelachowska
authors.forename: Krystyna
authors.initials: K
authors.lastname: Dabrowska
authors.forename: Aneta
authors.initials: A
authors.lastname: Kurzepa
authors.forename: Janusz
authors.initials: J
authors.lastname: Boratynski
authors.forename: Danuta
authors.initials: D
authors.lastname: Syper
authors.forename: Gryzelda
authors.initials: G
authors.lastname: Pozniak
authors.forename: Czeslaw
authors.initials: C
authors.lastname: Lugowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Gorski
mesh_terms: D017122:Bacteriophage T4 / Q000276:immunology*; D004731:Endotoxins / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D008163:Luminescent Measurements; D008165:Luminol / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000821:virology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D017382:Reactive Oxygen Species; D008165:Luminol