Superoxide generation and its modulation by adenosine in the neutrophils of subjects with asthma.
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.
Meltzer
S
S
Department of Allergy and Clinical Immunology, Kaiser Permanente Medical Center, Los Angeles, Calif 90027.
Goldberg
B
B
Lad
P
P
Easton
J
J
D000241:Adenosine / Q000494:pharmacology*; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000008:administration & dosage; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000096:biosynthesis* / Q000097:blood
D008688:Methacholine Compounds; D016210:Methacholine Chloride; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000241:Adenosine