The effect of fexofenadine on expression of intercellular adhesion molecule 1 and induction of apoptosis on peripheral eosinophils.
The role of eosinophils in the pathogenesis of allergic disorders has been established by several studies. Recently, it has been suggested that second-generation antihistamines, widely used to relieve allergic symptoms, may have anti-inflammatory effects. To assess the possible anti-inflammatory activity of fexofenadine, a selective H1-receptor antagonist, we evaluated its capacity to modulate the expression of adhesion molecules leukocyte function-associated antigen (LFA) 1 and intracellular adhesion molecule (ICAM) 1 on eosinophil surface and to induce apoptosis of eosinophils. To analyze the expression of adhesion molecules, eosinophils from healthy donors were cultured in the presence of interferon gamma and tumor necrosis factor alpha with various concentrations of fexofenadine, incubated with monoclonal antibodies anti-ICAM-1 and LFA-1 and then analyzed by flow cytometry. To evaluate apoptosis of eosinophils, cells stimulated with interleukin-5, in the presence of different concentrations of fexofenadine, have been incubated with a phosphatidylserine-binding protein (annexin V) fluorescein isothiocyanate conjugated and then analyzed by flow cytometry. Apoptosis was evaluated as a percentage of annexin V+ cells. In this study, fexofenadine did not cause any significant changes in the expression of LFA-1 but was shown to be able to inhibit the expression of ICAM-1 at concentrations between 10(-3) and 10(-4) M. Moreover, concentrations of fexofenadine from 10(-3) to 6 x 10(-4) M induced a significant increment in the percentage of apoptotic cells. Our findings indicate the possibility of obtaining relevant anti-inflammatory pharmacologic effects, other than antihistamine activity, by fexofenadine, such as inhibition of ICAM-1 expression and induction of eosinophil apoptosis.
Vancheri
Carlo
C
Department of Internal and Specialistic Medicine, Section of Respiratory Diseases, University of Catania, Via Passo Gravina 187, 95125 Catania, Italy.
Mastruzzo
Claudio
C
Tomaselli
Valerio
V
Bellistrì
Guglielmo
G
Pistorio
Maria Provvidenza
MP
Greco
Lucia Roberta
LR
Salinaro
Elisa Trovato
ET
Failla
Marco
M
Contrafatto
Maria Rita
MR
Crimi
Nunzio
N
D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000494:pharmacology
D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D006634:Histamine H1 Antagonists; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D016593:Terfenadine; C093230:fexofenadine