title: Biochemical mechanisms involved in the priming of neutrophils by tumor necrosis factor.
abstract: Preincubation of human neutrophils with recombinant tumor necrosis factor alpha has previously been shown by us to enhance superoxide production of neutrophils in response to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine, and the phorbol ester, phorbol myristate acetate. In this study, we further investigate the biochemical basis for this enhancement. We found that in neutrophils, TNF by itself does not induce: (1) an influx of sodium, (2) an alteration in activity or translocation of the calcium and phospholipid dependent protein kinase (C-kinase), or (3) a release of arachidonic acid from preloaded cells. TNF did, however, induce a time- and concentration-dependent increase in the phosphorylation of several neutrophil proteins, with the most dramatic concentration dependent increase in a 64,000 Da protein. Finally, the enhancement of O2 production by pretreatment of neutrophils with TNF was found to be independent of a pertussis toxin-sensitive guanine nucleotide regulatory protein.
authors.affiliation: Department of Pediatrics, University of Alabama, School of Medicine, Birmingham 35233.
authors.forename: R L
authors.initials: RL
authors.lastname: Berkow
authors.forename: M R
authors.initials: MR
authors.lastname: Dodson
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis; D012964:Sodium / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007546:Isoquinolines; D010879:Piperazines; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D037342:Pertussis Toxin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate