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Effects of theophylline on human eosinophil functions: comparative study with neutrophil functions
Author(s) -
Yasui Kozo,
Agematsu Kazunaga,
Shinozaki Koji,
Hokibara Sho,
Nagumo Haruo,
Yamada Shinji,
Kobayashi Norimoto,
Komiyama Atsushi
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.2.194
Subject(s) - theophylline , chemotaxis , adenosine receptor , eosinophil , biology , adenosine , antagonism , phosphodiesterase , granulocyte , receptor , bronchodilator , n formylmethionine leucyl phenylalanine , medicine , phosphodiesterase inhibitor , pharmacology , endocrinology , agonist , immunology , biochemistry , asthma , enzyme
The understanding of theophylline as a bronchodilator has been reconsidered in recent years. We undertook to determine its immunomodulatory actions in granulocytes and elucidate their mechanism. Preincubation of neutrophils with theophylline (10 ‐5 to 5 × 10 ‐3 M) had a biphasic effect on O 2 − production stimulated with N ‐formyl‐methionyl‐leucyl‐phenylalanine or C5a. Theophylline potentiates O 2 − production via adenosine A 2A receptor antagonism induced by receptor‐linked agonists from neutrophils, but not from eosinophils. The addition of theophylline caused a significant decline in neutrophil chemotaxis at lower concentrations than those for eosinophil motility. Theophylline reduces neutrophil chemotaxis via adenosine A 1 receptor antagonism. At high concentrations, with an intracellular cAMP accumulation as a result of phosphodiesterase (PDE) inhibition, theophylline also exerts an inhibitory effect on the O 2 − production and chemotaxis of both types of cells. The difference in theophylline’s effect on neutrophils and eosinophils appears to depend on the existence of specific adenosine receptors. Theophylline thus modulates granulocyte functions in association with specific adenosine receptor antagonism and cAMP‐PDE inhibition.