title: Mycophenolic acid inhibits PMA-induced activation of the neutrophil respiratory burst.
abstract: Mycophenolate mofetil (MMF) is commonly used in immunosuppressive regimens for solid organ transplantation. There is evidence that the hydrolyzed active agent mycophenolic acid (MPA) causes the endothelial depletion of intracellular guanosine 5'-triphosphate (GTP) levels. This depletion may cause inactivation of nicotinamide adenine dinucleotide phosphate oxidase. The purpose of the present study was to examine the impact of MPA on the neutrophil respiratory burst and phagocytic activity using flow cytometry. In whole blood of healthy volunteers, 2 different doses of MPA (1 and 10 mumol/L) did not alter hydrogen peroxide production of neutrophils induced by receptor-dependent activators. In contrast, MPA inhibits the protein kinase C (PKC)-mediated hydrogen peroxide production by phorbol 12-myristate 13-acetate (PMA) in a time-dependent manner (negative: 21.17 +/- 1.64 vs. 120 min: 14.46 +/- 1.28 mean fluorescence intensity, incubation with 1 mumol/L MPA). In conclusion, our results corroborated that the neutrophil respiratory burst activity of healthy volunteers, induced by either formyl-methionyl-leucylphenylalanine (fMLP), priming with tumor necrosis factor alpha followed by fMLP or Escherichia coli and neutrophil phagocytic capacity, were not significantly affected after MPA treatment. We also could demonstrate that the hydrogen peroxide production of neutrophils decreased in response to the PKC activator PMA in a time-dependent manner.
authors.affiliation: Department of Anesthesiology, Hannover Medical School, Hannover, Germany. juettner.bjoern@mh-hannover.de
authors.forename: B
authors.initials: B
authors.lastname: Jüttner
authors.forename: M
authors.initials: M
authors.lastname: Bencel
authors.forename: A
authors.initials: A
authors.lastname: Weissig
authors.forename: A
authors.initials: A
authors.lastname: Studzinski
authors.forename: K
authors.initials: K
authors.lastname: Stenger
authors.forename: D
authors.initials: D
authors.lastname: Scheinichen
mesh_terms: D000328:Adult; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D009173:Mycophenolic Acid / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D006861:Hydrogen Peroxide; D009173:Mycophenolic Acid; D013755:Tetradecanoylphorbol Acetate