title: ATP inhibits hydroxyl radical formation and the inflammatory response of stimulated whole blood even under circumstances of severe oxidative stress.
abstract: We recently reported that Adenosine-5'-triphosphate (ATP) is able to inhibit the inflammatory reaction in stimulated whole blood. Many diseases, in which inflammatory reactions are involved, are associated with oxidative stress. In the present study, we therefore, investigated the effect of ATP on cytokine release in stimulated whole blood under conditions of oxidative stress, as simulated by pre-incubation of blood with hydrogen peroxide (H(2)O(2)). In the presence of H(2)O(2), ATP at concentrations of 100 and 300 microM inhibited Tumour Necrosis factor-alpha (TNF-alpha) release and stimulated IL-10 release in LPS-PHA stimulated whole blood. Moreover, electron spin resonance (ESR) measurements showed that ATP and its breakdown product Adenosine-5'-diphosphate (ADP) attenuated spin trap-hydroxyl radical adduct formation in the Fenton reaction. Our results demonstrate that even in circumstances of severe oxidative stress, ATP has marked anti-inflammatory properties in stimulated whole blood. Moreover, the inhibition of the hydroxyl radical ESR signal indicates a direct attenuation of oxidative stress by ATP.
authors.affiliation: Department of Epidemiology, NUTRIM, Maastricht University, P.O. Box 616 6200 MD, The Netherlands. e.swennen@farmaco.unimaas.nl
authors.forename: Els L R
authors.initials: EL
authors.lastname: Swennen
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000328:Adult; D001769:Blood / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001773:Blood Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D017665:Hydroxyl Radical; D000255:Adenosine Triphosphate