title: Priming of the neutrophil respiratory burst is species-dependent and involves MAP kinase activation.
abstract: BACKGROUND
  Priming of the neutrophil respiratory burst has been implicated in the pathogenesis of multi-system organ failure (MSOF) after sepsis and trauma. The intracellular signal transduction pathways that mediate priming are unclear.
  
  
  METHODS
  Human, porcine, rabbit, rat, and mouse neutrophils were assayed by luminol-dependent chemiluminescence in whole blood and purified neutrophil preparations. Multiple priming agents and agonists were studied, as was inhibition of priming by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and the Mek 1/2 inhibitor PD98059.
  
  
  RESULTS
  Priming by tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly inhibited by SB203580, whereas platelet-activating factor (PAF) priming was unaffected. Neither TNF-alpha nor PAF primed polymorphonuclear neutrophils (PMNs) within whole blood for N-formyl-methionyl-leucyl-phenylalanine (f-MLP) activation, in contrast to activation by complement-opsonized zymosan (OPZ) or low-dose phorbolmyristate acetate (PMA). Both TNF-alpha and PAF, however, primed purified neutrophils for f-MLP activation. In contrast to human and porcine PMNs, rabbit, rat, and mouse PMNs could not be primed by TNF-alpha or PAF, regardless of the final agonist.
  
  
  CONCLUSIONS
  Priming of the PMN respiratory burst proceeds through multiple signaling pathways, depending on the particular priming agent and agonist pair. Differences in priming between PMNs in whole blood and purified preparations may be physiologically significant. There is a pronounced species dependency in the ability to prime the neutrophil respiratory burst.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Mass., USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Yaffe
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: P A
authors.initials: PA
authors.lastname: Burke
authors.forename: R A
authors.initials: RA
authors.lastname: Forse
authors.forename: G E
authors.initials: GE
authors.lastname: Brown
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D016897:Respiratory Burst; D015398:Signal Transduction; D013045:Species Specificity; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate