Inhibition of Fc gamma R- and CR-mediated human neutrophil chemiluminescent responses by anti-allergic and anti-histaminergic drugs.

The effects of ketotifen fumarate (KF) and clemastine fumarate (CF) on neutrophil chemiluminescent (CL) responses to zymosan particles coated with either IgG (IgGZ), C3 (C3Z), or both (IC3Z), were examined in vitro. These opsonized zymosans caused not only detectable neutrophil superoxide anion generation evaluated by an MCLA-dependent CL (MDCL) assay, with the order of light emission being IC3Z > IgGZ > C3Z, but also a transient rise of neutrophil [Ca2+]i measured by an aequorin-dependent CL (ADCL) assay. Both KF and CF could suppress all opsonized zymosan-induced neutrophil MDCL in a dose-dependent fashion, but not all ADCL. Similar inhibitory effects of KF and CF were observed on the phorbol myristate acetate-induced MDCL. However, there was no interference by these two drugs with the measurement of MDCL in the hypoxanthine/xanthine oxidase superoxide anion generation system. These results indicate that the inhibitory effects of both KF and CF on Fc gamma R- and/or CR-mediated neutrophil oxidative potential is attributable to effects on an enzymatic reaction after protein kinase C activation in the oxidative signal transduction pathway.