IL-3-INDUCED HISTAMINE-RELEASE FROM HUMAN BASOPHILS - DISSOCIATION FROM CATIONIC DYE BINDING AND DOWN-REGULATION BY NA+ AND K+

The effect of recombinant human IL-3 on human basophils from normal su bjects was evaluated by the decrease of toluidine blue-positive basoph ils (TB+) and by histamine release. IL-3 (0.001 to 100 ng) caused the decrease of TB+ without concomitant histamine release, whereas anti-Ig E-induced TB+ decrease was accompanied by histamine release. IL-3 enha nced both anti-IgE-induced TB+ decrease and histamine release. IL-3-in duced TB+ decrease was dose- and Ca2(+)-dependent and related to the t ime of incubation (detectable after an incubation of 5 min and maximal after incubation of 2 h). When extracellular Na+ was replaced isosmot ically with choline, N-methyl-D-glucamine, or glucose, histamine relea se also was observed after direct stimulation with IL-3. The effect wa s dose dependent, related to the time of incubation (detectable after 30 min and maximal after 60 min), and required extracellular Ca2+. The increase in extracellular Na+ or K+ concentrations was accompanied by a reduction of histamine release, with a more marked effect on IL-3- than on anti-IgE-induced histamine release. In line with these results , the Na+ ionophore gramicidin D, which increases Na+ influx, and the K+ channel blocker 4-aminopyridine, which decreases K+ efflux, dose-de pendently inhibited anti-IgE- and IL-3-induced histamine release. The inhibitory effects of Na+ and K+ were slightly additive, suggesting an action via the same pathway, which most probably is membrane potentia l. These results indicate that: 1) IL-3 can induce TB+ decrease withou t concomitant histamine release, 2) basophils from normal subjects can release histamine on challenge with IL-3 once the inhibitory effect o f Na+ is removed, and 3) Na+ and K+ down-regulate IL-3- as well as ant i-IgE-induced histamine release.