Superoxide generation and its modulation by adenosine in the neutrophils of subjects with asthma.

Abstract

Airway inflammation with neutrophil infiltration may play a role in airway hyperreactivity. Neutrophils may exert their effects through the generation of superoxide O2- anion and other oxygen-derived free radicals. O2- generation by neutrophils has been demonstrated to be modulated by adenosine at physiologic concentrations. Therefore, we have investigated the function of peripheral blood neutrophils with respect to O2- anion generation and its regulation by adenosine in both subjects with asthma and normal subjects and also the relationship between O2- anion generation and airway hyperresponsiveness in subjects with asthma. Purified neutrophils were obtained from eight subjects with stable asthma and seven normal control subjects not taking chronic medications. O2- anion generation in subjects with asthma was significantly higher compared with that of normal subjects after stimulation with either N-formyl-methionyl-leucyl-phenylalanine (mean, 14.8 nmol/10(6) cells for subjects with asthma versus mean, 9.6 nmol/10(6) cells for normal subjects; p less than 0.01) or phorbol myristate acetate (mean, 13.6 nmol/10(6) cells versus mean, 8.1 nmol/10(6) cells; p less than 0.05). Adenosine inhibited N-formyl-methionyl-leucyl-phenylalanine-stimulated O2- anion generation in a dose-related fashion in subjects with asthma and normal subjects to a similar degree. Adenosine had no effect on O2- anion generation after phorbol myristate acetate stimulation. These results indicate that neutrophils from subjects with asthma produce more O2- anion when they are stimulated than do neutrophils from normal subjects and that this difference is not due to adenosine modulation. In subjects with asthma, O2- anion generation correlated with the degree of airway hyperresponsiveness to inhaled methacholine.

• Authors: S Meltzer, B Goldberg, P Lad, J Easton
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 83 Issue 5 Pg. 960-6 (May 1989) ISSN: 0091-6749 [Print] United States
• PMID: 2541190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Methacholine Compounds
• Methacholine Chloride
• Superoxides
• N-Formylmethionine Leucyl-Phenylalanine
• Adenosine

Topics

• Adenosine (pharmacology)
• Administration, Inhalation
• Adolescent
• Adult
• Asthma (blood)
• Female
• Humans
• Male
• Methacholine Chloride
• Methacholine Compounds (administration & dosage)
• Middle Aged
• N-Formylmethionine Leucyl-Phenylalanine
• Neutrophils (drug effects, metabolism)
• Superoxides (biosynthesis, blood)