Aminophylline induced oxidative metabolism in isolated canine polymorphonuclear leukocytes.
Adenosine 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 aminophylline and theophylline inhibit the cyclic nucleotide phosphodiesterase of smooth muscle, reversing pathogenic states of bronchoconstriction. 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 direct in vitro activation of isolated canine neutrophils it may have the capacity to potentiate neutrophil activation in 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. H202 induction by aminophylline 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 pathogenicity and tissue damage by indiscriminantly releasing oxygen-reactive species.
Gruber
D F
DF
Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20814-5145.
O'Halloran
K P
KP
Farese
A M
AM
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D005453:Fluorescence; D006861:Hydrogen Peroxide / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism*; D010084:Oxidation-Reduction; D012015:Reference Standards; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000628:Aminophylline; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate