Asthmatic patients have neutrophils that exhibit diminished responsiveness to adenosine.
Activation of neutrophils (PMN) within the airways results in the secretion of a number of products such as reduced oxygen metabolites that could contribute to the inflammatory response associated with asthma. However, mediators of allergy, such as histamine, prostaglandin E2 (PGE2), isoproterenol, and adenosine, may serve to mitigate this inflammation through feedback inhibition of neutrophil function. To test the hypothesis that PMN activation and feedback inhibition mechanisms may be abnormal in asthmatics, we compared both superoxide production and adenosine-induced suppression of superoxide production in 12 matched pairs of asthmatics and control subjects. PMN obtained from asthmatic patients generated significantly more superoxide in response to f-met-leu-phe (fMLP) than controls (2.94 +/- 55 nmol/5 x 10(5) PMN/5 min versus 1.38 +/- 0.35 at 2 x 10(-8) M fMLP and 3.81 +/- 0.68 nmol versus 2.04 +/- 0.45 nmol at 10(-7) M; p less than 0.01 for both). In contrast, the respiratory burst generated by two receptor-independent stimuli, the calcium ionophore A23187 and phorbol myristate acetate, was equivalent between control and asthmatic subjects. At 10(-6) M, 2-chloroadenosine induced a 19.5 +/- 5.1% inhibition of fMLP-stimulated superoxide production in PMN from patients with asthma as compared to 55.6 +/- 24.6% inhibition in PMN from control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Sustiel
A M
AM
Department of Medicine, New England Medical Center Hospital, Tufts Medical School, Boston, Massachusetts.
Joseph
B
B
Rocklin
R E
RE
Borish
L
L
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D000001:Calcimycin / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
D008070:Lipopolysaccharides; D013481:Superoxides; D015762:2-Chloroadenosine; D000001:Calcimycin; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042205:methionyl-leucyl-phenylalanine; D000241:Adenosine; D015232:Dinoprostone; D007545:Isoproterenol