title: Inhibition of neutrophil priming and tyrosyl phosphorylation by cepharanthine, a nonsteroidal antiinflammatory drug.
abstract: Receptor-mediated superoxide (O2.-)-generation and tyrosyl phosphorylation of neutrophil proteins, such as 58, 65, 84, 108 and 115 kDa, were enhanced by priming cells with granulocyte colony stimulating factor (G-CSF) [Akimura, K. et al. Arch. Biochem. Biophys. 298: 703-709, 1992]. To elucidate the possible involvement of tyrosyl phosphorylation of neutrophil proteins in the enhancing mechanism of O2.- generation, the effect of cepharanthine, a biscoclaurine alkaloid that inhibits phorbol 12-myristate 13-acetate (PMA)- and receptor-mediated O2.- generation, on the priming of human peripheral neutrophils (HPPMN) was studied. Both enhancement of formyl-methionyl-leucyl- phenylalanine (FMLP)-mediated O2.- generation and tyrosyl phosphorylation of some neutrophil proteins, i.e., 115, 108 and 84 kDa proteins, by HHPMN after treatment with G-CSF were strongly inhibited by cepharanthine in a concentration- and treatment-time-dependent manner. In contrast, inhibition of PMA-mediated O2.- generation by cepharanthine was weak and independent of treatment time. These results suggest that cepharanthine might inhibit the priming step of neutrophil activation concomitantly with its inhibition of the tyrosyl phosphorylation of some neutrophil proteins that might underlie the mechanism for priming of neutrophils with G-CSF.
authors.affiliation: Department of Cell Chemistry, Okayama University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kobuchi
authors.forename: M J
authors.initials: MJ
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Matsuno
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
authors.forename: K
authors.initials: K
authors.lastname: Utsumi
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D017305:Annexin A1 / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D044182:Benzylisoquinolines; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D052117:Benzodioxoles
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids; D017305:Annexin A1; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D004815:Epidermal Growth Factor; D016179:Granulocyte Colony-Stimulating Factor; D007546:Isoquinolines; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010100:Oxygen; D010879:Piperazines; D011505:Protein-Tyrosine Kinases; D014409:Tumor Necrosis Factor-alpha; C006947:cepharanthine; D052117:Benzodioxoles