INHIBITORY EFFECTS OF AZELASTINE HYDROCHLORIDE ON CA2-CELL LINE EOL-1( INFLUX, ACTIN POLYMERIZATION AND RELEASE OF EOSINOPHIL CATIONIC PROTEIN OF AN EOSINOPHILIC LEUKEMIA)

The inhibitory effects of azelastine hydrochloride on PAF-induced and fMLP-induced Ca2+ influx, actin polymerization and calcium ionophore A 23187-induced and aggregated IgG-induced release of eosinophil cationi c protein (ECP) of an eosinophilic leukaemia cell line, EoL-1, were ex amined EoL-1 cells cultured with 0.2 mM dibutyryladenosine-cyclic mono phosphate for 48 hours showed an increase in intracellular free Ca2+ c oncentration ([Ca2+]i) and actin polymerization when stimulated by PAF and fMLP. Azelastine hydrochloride inhibited PAF-induced and fMLP-ind uced Ca2+ influx ([Ca2+]i) in a dose-dependent manner with an IC50 of 1 x 10(-8) M and 1 x 10(-7)M, respectively. It also inhibited PAF-indu ced and fMLP-induced actin polymerization in a dose-dependent manner u p to 40% and 30% respectively. EoL-1 cells were differentiated to cont ain ECP in their eosinophilic granules when cultured for 9 days with s upernatants of a human adult T cell leukaemia cell line, HIL-3 (HIL-3 sup). Calcium ionophore A23187 and aggregated IgG induced the secretio n of ECP by EoL-1 cells. Azelastine hydrochloride inhibited the secret ion of ECP in a dose-dependent manner These inhibitory effects were se en even at therapeutic concentrations of 10(-8) M to 10(-9) M. These r esults indicate that the therapeutic effects of azelastine hydrochlori de as an anti-allergic agent may include inhibition of the accumulatio n of eosinophils into the locus of allergic inflammation and of the re lease of cytotoxic granules from eosinophils.