Time-dependent effects of ATP and its degradation products on inflammatory markers in human blood ex vivo.
We recently reported that adenosine 5'-triphosphate (ATP) modulates cytokine release in lipopolysaccharide (LPS)-phytohemagglutinin (PHA)-stimulated blood. ATP inhibited tumor necrosis factor-alpha (TNF-alpha) release via activation of the P2Y(11) receptor and increased interleukin (IL)-10 release via stimulation of the P2Y(12) receptor. Because ATP is known to be broken down by various ecto-enzymes, we determined the degradation profile of ATP in time in LPS-PHA-stimulated blood. ATP slowly metabolized with 14% remaining after 6h. Simultaneously, adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP) and hypoxanthine were formed. Subsequently, we investigated the time-dependent effects of ATP and its metabolites on inflammatory markers. Results showed that ATP decreased the rise in concentrations of TNF-alpha, interferon-gamma (IFN-gamma) and IL-1beta, but increased concentrations of IL-8 and IL-10. Metabolites of ATP showed either no, similar or opposite effects on cytokine release, compared to ATP. In conclusion, ATP has rapid immunomodulatory effects on a variety of cytokines in stimulated whole blood that persist until 24h.
Swennen
Els L R
EL
Department of Epidemiology, NUTRIM, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. e.swennen@farmaco.unimaas.nl
Coolen
Erik J C M
EJ
Arts
Ilja C W
IC
Bast
Aalt
A
Dagnelie
Pieter C
PC
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000276:immunology* / Q000493:pharmacokinetics*; D000328:Adult; D000954:Antigens, Surface / Q000187:drug effects*; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000502:physiology; D066298:In Vitro Techniques; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D016753:Interleukin-10 / Q000819:agonists / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000276:immunology / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000954:Antigens, Surface; D007155:Immunologic Factors; D008070:Lipopolysaccharides; C109734:P2RY11 protein, human; C548576:P2RY12 protein, human; D010835:Phytohemagglutinins; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D014409:Tumor Necrosis Factor-alpha; C433788:lipopolysaccharide, E. coli O26-B6; D016753:Interleukin-10; D000255:Adenosine Triphosphate