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Inflammation Research

, Volume 48, Issue 11, pp 594–601 | Cite as

High concentrations of histamine stimulate equine polymorphonuclear neutrophils to produce reactive oxygen species

  • H. Benbarek
  • A. Mouithys-Mickalad
  • G. Deby-Dupont
  • C. Deby
  • S. Grülke
  • A. Nemmar
  • M. Lamy
  • D. Serteyn

Abstract.

Objective and Design: Because high concentrations of histamine are locally released in inflammation, we investigated the effects of supraphysiological doses of histamine on the production of reactive oxygen species (ROS) by neutrophils. ¶Materials and Methods: Isolated equine neutrophils were activated by 10-4 to 5 × 10-3 M histamine. The production of ROS and free radicals was estimated by luminol-enhanced chemiluminescence (CL) and electron spin resonance (ESR) with spin trapping technique. In this model of histamine-stimulated neutrophils, we tested the antagonists of H1 and H2 histamine receptors, the role of Ca2+ and Mg2+, the role of staurosporine and pertussis toxin (inhibitors of protein kinase C and proteins G) and the effects of superoxide dismutase, catalase, hydroxyl radical scavengers (phenylalanine and mannitol) and NG-monomethyl-L-arginine (L-NMMA), inhibitor of NO-synthase. ¶Results: Histamine (from 10-5 to 10-3 M) stimulated neutrophils to produce CL and ESR signals characterized by spin adducts of superoxide anion and/or hydroxyl radicals. The CL response was inhibited by 10-4 and 10-3 M H1 receptor antagonists (promethazine, pyrilamine, and diphenhydramine), by Ca2+ and Mg2+ depletion and by 10 nmoles staurosporine. CL was partially inhibited by pertussis toxin (4 μg/ mL). The ESR signals were practically suppressed by pyrilamine (an H1 receptor antagonist) and superoxide dismutase, and partially inhibited by catalase, hydroxyl radical scavengers and L-NMMA (respectively 59, ± 30% and 68% inhibition). ¶Conclusions: High concentrations of histamine stimulated the neutrophils to product ROS and free radicals via H1 receptors and the NADPH-oxidase pathway.

Key words: Histamine — Equine neutrophils — Chemiluminescence — Electron spin resonance — Free radical 

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Copyright information

© Birkhäuser Verlag, Basel, 1999

Authors and Affiliations

  • H. Benbarek
    • 1
  • A. Mouithys-Mickalad
    • 2
  • G. Deby-Dupont
    • 2
  • C. Deby
    • 2
  • S. Grülke
    • 1
  • A. Nemmar
    • 1
  • M. Lamy
    • 2
  • D. Serteyn
    • 1
  1. 1.Anesthésiologie Générale et Pathologie Chirurgicale des Grands Animaux, Faculté de Médecine Vétérinaire, B44, Université de Liège, Domaine Universitaire du Sart Tilman, B-4000 Liège, Belgique BE
  2. 2.Centre for Oxygen Research and Development, Institut de Chimie, B6a, Université de Liège, Domaine Universitaire du Sart Tilman, B-4000 Liège, Belgique, Fax +3243662866, e-mail: cbo@ulg.ac.be, gdeby@ulg.ac.beBE

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