Effects of theophylline on human eosinophil functions: comparative study with neutrophil functions.
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 x 10(-3) M) had a biphasic effect on O2(-) production stimulated with N-formyl-methionyl-leucyl-phenylalanine or C5a. Theophylline potentiates O2(-) 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 A1 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 O2(-) 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.
Yasui
K
K
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan. koyasui@gipac.shinshu-u.ac.jp
Agematsu
K
K
Shinozaki
K
K
Hokibara
S
S
Nagumo
H
H
Yamada
S
S
Kobayashi
N
N
Komiyama
A
A
D001993:Bronchodilator Agents / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology*
D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D018047:Receptors, Purinergic P1; D013481:Superoxides; D013806:Theophylline