Aminophylline Induced Oxidative Metabolism in Isolated Canine Polymorphonuclear Leukocytes
作者:
GruberDale F.,
O'halloranKevin P.,
FareseAnn M.,
期刊:
Immunopharmacology and Immunotoxicology
(Taylor Available online 1989)
卷期:
Volume 11,
issue 2-3
页码: 151-163
ISSN:0892-3973
年代: 1989
DOI:10.3109/08923978909005362
出版商: Taylor&Francis
数据来源: Taylor
摘要:
AbstractAdenosine reportedly mediates myocardial and skeletal blood flow, bronchoconstriction, and cellular production of toxic oxygen radicals. Cellular effects of adenosine can be antagonized by the methylxanthines, which are widely used in the clinical treatment of obstructive airway diseases. Methylxanthine compounds such as aminophyl-line and theophylline inhibit the cyclic nucleotide phosphodiesterase of smooth muscle, reversing pathogenic states of bronchoconstr ict ion. Recent techniques in -flow cytometry allow examination of individual cells -for the electrophysiological and metabolic cellular side effects of methylxanthine therapy. We report that the flow cytometric examination of isolated canine peripheral neutrophils, in the presence of therapeutic concentrations of aminophylline resulted in small but significant membrane depolarization and almost fivefold increases in baseline cytosolic H202 levels. If aminophylline is capable of directin vitroactivation of isolated canine neutrophils it may have the capacity to potentiate neutrophil activationin vivo: indirectly by competing with circulating modifiers, such as adenosine, for cell surface receptor sites and directly by the induction of toxic oxygen radicals as demonstrated here. H2O2 induction by aminophyl-line and other xanthine derivatives may become clinically important in instances of vascular occlusion, stasis, or instances of reperfusion where neutrophils may become activated. In an activated state, neutrophils could contribute to pathogenecity and tissue damage by indiscrimin-antly releasing oxygen-reactive species.
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