PMID- 19302273 OWN - NLM STAT- MEDLINE DCOM- 20091001 LR - 20131121 IS - 1399-3062 (Electronic) IS - 1398-2273 (Linking) VI - 11 IP - 3 DP - 2009 Jun TI - Mycophenolic acid inhibits PMA-induced activation of the neutrophil respiratory burst. PG - 235-40 LID - 10.1111/j.1399-3062.2009.00382.x [doi] AB - 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. FAU - Juttner, B AU - Juttner B AD - Department of Anesthesiology, Hannover Medical School, Hannover, Germany. juettner.bjoern@mh-hannover.de FAU - Bencel, M AU - Bencel M FAU - Weissig, A AU - Weissig A FAU - Studzinski, A AU - Studzinski A FAU - Stenger, K AU - Stenger K FAU - Scheinichen, D AU - Scheinichen D LA - eng PT - Journal Article DEP - 20090315 PL - Denmark TA - Transpl Infect Dis JT - Transplant infectious disease : an official journal of the Transplantation Society JID - 100883688 RN - BBX060AN9V (Hydrogen Peroxide) RN - HU9DX48N0T (Mycophenolic Acid) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Adult MH - Female MH - Flow Cytometry MH - Humans MH - Hydrogen Peroxide/metabolism MH - Male MH - Mycophenolic Acid/*pharmacology MH - Neutrophils/*drug effects/immunology/metabolism MH - Phagocytosis/*drug effects MH - Respiratory Burst/*drug effects MH - Tetradecanoylphorbol Acetate/*pharmacology MH - Young Adult EDAT- 2009/03/24 09:00 MHDA- 2009/10/02 06:00 CRDT- 2009/03/24 09:00 PHST- 2009/03/24 09:00 [entrez] PHST- 2009/03/24 09:00 [pubmed] PHST- 2009/10/02 06:00 [medline] AID - TID382 [pii] AID - 10.1111/j.1399-3062.2009.00382.x [doi] PST - ppublish SO - Transpl Infect Dis. 2009 Jun;11(3):235-40. doi: 10.1111/j.1399-3062.2009.00382.x. Epub 2009 Mar 15.