Biochemical mechanisms involved in the priming of neutrophils by tumor necrosis factor.
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.
Berkow
R L
RL
Department of Pediatrics, University of Alabama, School of Medicine, Birmingham 35233.
Dodson
M R
MR
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
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