Theophylline Attenuates the Adhesion of Eosinophils to Endothelial Cells

Abstract

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-α. Conclusion: 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.

Interferon-β augments eosinophil adhesion-inducing activity of endothelial cells

“…The expression of VCAM-1 and ICAM-1 was determined by cell ELISA, as previously reported [20,24]. Briefly, the HUVEC monolayers were incubated in the 96-well tissue culture plates and then stimulated with either a combination of IFN-b (30-1,000 pM) and TNF-a (10 pM) or with IFN-b (30-1,000 pM) alone at 37uC for 24 h [20,24].…”

“…Briefly, the HUVEC monolayers were incubated in the 96-well tissue culture plates and then stimulated with either a combination of IFN-b (30-1,000 pM) and TNF-a (10 pM) or with IFN-b (30-1,000 pM) alone at 37uC for 24 h [20,24]. Prior to the evaluation, HUVECs were washed and incubated at 37uC for 30 min with a blocking buffer (PBS containing 5% NCS and 3% nonfat dry milk).…”

Theophylline Attenuates the Neutrophil-Dependent Augmentation of Eosinophil Trans-Basement Membrane Migration

“…Finally, Lim et al [3] reported that theophylline reduced the number of eosinophils in sputa, biopsied specimens, and bronchoalveolar lavage fluids in mild asthmatic patients. Theophylline actually possesses a variety of in vitro effects on human eosinophils: induction of apoptosis [4, 5], inhibition of degranulation [5,6,7] and cell migration [8], and reduction of the surface expression of CD11b [6, 7, 9] or CD4 [8]. In this context, we have reported that theophylline attenuates eosinophil adhesion to endothelial cells in vitro at a clinically therapeutic concentration [9].…”

“…Theophylline actually possesses a variety of in vitro effects on human eosinophils: induction of apoptosis [4, 5], inhibition of degranulation [5,6,7] and cell migration [8], and reduction of the surface expression of CD11b [6, 7, 9] or CD4 [8]. In this context, we have reported that theophylline attenuates eosinophil adhesion to endothelial cells in vitro at a clinically therapeutic concentration [9]. Furthermore, theophylline inhibits the expression of ICAM-1 and VCAM-1 on endothelial cells which had been stimulated with interleukin-4 (IL-4) plus tumor necrosis factor-α (TNF-α) [9, 10].…”

“…In this context, we have reported that theophylline attenuates eosinophil adhesion to endothelial cells in vitro at a clinically therapeutic concentration [9]. Furthermore, theophylline inhibits the expression of ICAM-1 and VCAM-1 on endothelial cells which had been stimulated with interleukin-4 (IL-4) plus tumor necrosis factor-α (TNF-α) [9, 10]. Thus, theophylline possibly exerts an inhibitory effect on both the adhesive property of eosinophils and the expression of adhesion molecules on endothelial cells [9, 10].…”