Effect of theophylline on CD11b and L-selectin expression and density of eosinophils and neutrophils in vitro.
The nonspecific phosphodiesterase inhibitor theophylline, widely used in asthma therapy, may cause a decrease in inflammatory responses of airways. In asthma, eosinophils migrate to the airway wall and become activated. Activated eosinophils are characterized by low cell density, as well as increased expression of CD11b and reduced expression of L-selectin, two adhesion molecules involved in transendothelial migration. To study the anti-inflammatory effect of theophylline on granulocyte adhesion molecules in vitro, the platelet-activating factor (PAF)-induced density shift was determined by density centrifugation and the modulation of CD11b and L-selectin expression by flow cytometry on eosinophils and neutrophils in human whole blood. A relatively high concentration of theophylline (10(-3) M) inhibited the increase in the percentage of hypodense eosinophils and neutrophils in whole-blood samples after PAF stimulation in vitro. A more pharmacological concentration (10(-4) M) inhibited the CD11b upregulation and L-selectin shedding induced by PAF (10(-7) M) on both eosinophils and neutrophils. The effect of isoproterenol on the inhibitory effect of theophylline was mainly additive, but a small synergistic effect could not be excluded. In conclusion theophylline can attenuate eosinophil and neutrophil activation in vitro at the level of adhesion molecule expression and changes in cell density. This may have implications for transendothelial migration of these cells in asthma.
Dept of Allergology, University Hospital Groningen, The Netherlands.
F M
FM
Spoelstra
C
C
Berends
B
B
Dijkhuizen
J G
JG
de Monchy
H F
HF
Kauffman
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D001249:Asthma / Q000097:blood* / Q000188:drug therapy; D001772:Blood Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D019041:L-Selectin / Q000096:biosynthesis* / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000096:biosynthesis* / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013806:Theophylline / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D016177:Macrophage-1 Antigen; D010726:Phosphodiesterase Inhibitors; D010972:Platelet Activating Factor; D019041:L-Selectin; D013806:Theophylline; D007545:Isoproterenol