Theophylline attenuates the adhesion of eosinophils to endothelial cells.
BACKGROUND
Bronchial asthma is characterized by infiltration of eosinophils and other inflammatory cells into the airways. Binding to adhesion molecules expressed on endothelial cells is an initial step of eosinophil accumulation in the airways of asthmatic patients. Theophylline has been widely used in the treatment of bronchial asthma mainly due to its bronchodilating effect. It has recently been suggested that theophylline induces modulating effects on the survival or functional status of eosinophils. The objective of this study was to determine whether theophylline modifies the adhesive interaction between eosinophils and endothelial cells.


METHODS
Eosinophils were isolated from blood of patients with mild asthma. The effects of theophylline on eosinophil adhesion to human umbilical vein endothelial cells (HUVEC) or recombinant adhesion proteins were evaluated. The effect of theophylline on the expression of adhesion molecules on HUVEC was also examined.


RESULTS
Theophylline significantly inhibited the eosinophil adhesion induced by formyl-methionyl-leucil-phenylalanine (FMLP) or interleukine-5 (IL-5) at a concentration within the therapeutic range. The effect of theophylline on eosinophil adhesion was mimicked by rolipram, a selective phosphodiesterase inhibitor, and N6,2'-O-dibutyladenosine 3'5'-cyclic monophosphate (Db-cAMP; cAMP analogue). Finally, theophylline inhibited the expression of ICAM-1 and VCAM-1 on HUVEC stimulated with IL-4 plus TNF-alpha.


CONCLUSIONS
Theophylline showed inhibitory effects on both the adhesive property of eosinophils and the expression of adhesion molecules on endothelial cells, thus suggesting that theophylline attenuates the adhesive interaction between eosinophils and endothelial cells.
Choo
Jae Hong
JH
Pulmonary Division, Second Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
Nagata
Makoto
M
Sutani
Akihisa
A
Kikuchi
Izumi
I
Sakamoto
Yoshio
Y
D000328:Adult; D001249:Asthma / Q000097:blood / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects; D020889:Rolipram / Q000494:pharmacology; D013806:Theophylline / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects
D001993:Bronchodilator Agents; D015848:Interleukin-5; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013806:Theophylline; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D020889:Rolipram