EFFECT OF THEOPHYLLINE ON CD11B AND L-SELECTIN EXPRESSION AND DENSITYOF EOSINOPHILS AND NEUTROPHILS IN-VITRO

The nonspecific phosphodiesterase inhibitor theophylline, widely used in asthma therapy, may cause a decrease in inflammatory responses of a irways, In asthma, eosinophils migrate to the airway wall and become a ctivated, 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 migratio n, To study the anti-inflammatory effect of theophylline on granulocyt e adhesion molecules in vitro, the platelet-activating factor (PAF)-in duced density shift was determined by density centrifugation and the m odulation of CD11b and L-selectin expression by how cytometry on eosin ophils and neutrophils in human whole blood, A relatively high concent ration of theophylline (10(-3) M) inhibited the increase in the percen tage of hypodense eosinophils and neutrophils in whole-blood samples a fter PAF stimulation in vitro. A more pharmacological concentration (1 0(-4) M) inhibited the CD11b upregulation and L-selectin shedding indu ced by PAF (10(-7) M) on both eosinophils and neutrophils. The effect of isoproterenol on the inhibitory effect of theophylline was mainly a dditive, but a small synergistic effect could not be excluded, In conc lusion 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 migratio n of these cells in asthma.