Effect of beta-adrenergic agents on human neutrophil granulocyte activation with N-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate

Pharmacol Toxicol. 1993 Apr-May;72(4-5):221-8. doi: 10.1111/j.1600-0773.1993.tb01640.x.

Abstract

Generation of reactive oxygen intermediates by activated polymorphonuclear neutrophil granulocytes plays an important role in development of microcirculatory injury. The effect of the beta 2-adrenergic receptor agonists (beta 2-agonists) isoprenaline and terbutaline on the chemiluminescence or oxygen consumption of human granulocytes in response to activation with n-formyl-methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA) was examined. The beta 2-agonist effect on activated cell aggregation and volume change was examined as well. As E. Coli lipopolysaccharide and FMLP may prime granulocytes for enhanced generation of reactive oxygen intermediates in response to other activators, the effect of beta 2-agonists on the priming effect of these agents was also investigated.

Results: 1) Optimal concentrations of beta 2-agonists decrease the human granulocyte generation of reactive oxygen intermediates in response to activation with FMLP by 40-60%, without affecting the response to PMA. 2) beta 2-Agonists modify the priming effect of FMLP on activation with PMA, but do not interfere with the priming effect of E. Coli lipopolysaccharide on activation with FMLP. 3) Isoprenaline have different effects on generation of reactive oxygen intermediates and cell aggregation in FMLP-activated granulocytes. 4) High concentrations of isoprenaline and terbutaline have contrasting non-specific effects on the chemiluminescence, but not on the oxygen consumption, of activated granulocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Cell Aggregation
  • Cell Count
  • Humans
  • Isoproterenol / pharmacology
  • Lipopolysaccharides / pharmacology
  • Luminescent Measurements
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology*
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Oxygen Consumption
  • Reactive Oxygen Species / metabolism
  • Terbutaline / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology*

Substances

  • Adrenergic beta-Agonists
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • N-Formylmethionine Leucyl-Phenylalanine
  • Isoproterenol
  • Terbutaline
  • Tetradecanoylphorbol Acetate