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The Journal of Immunology, Vol 155, Issue 5 2652-2660, Copyright © 1995 by American Association of Immunologists
ARTICLES |
A Tedeschi, M Palella, N Milazzo, M Lorini and A Miadonna
Department of Internal Medicine, University of Milan, IRCCS Ospedale Policlinico, Italy.
The effect of recombinant human IL-3 on human basophils from normal subjects was evaluated by the decrease of toluidine blue-positive basophils (TB+) and by histamine release. IL-3 (0.001 to 100 ng) caused the decrease of TB+ without concomitant histamine release, whereas anti- IgE-induced TB+ decrease was accompanied by histamine release. IL-3 enhanced both anti-IgE-induced TB+ decrease and histamine release. IL-3- induced TB+ decrease was dose- and Ca2+-dependent and related to the time of incubation (detectable after an incubation of 5 min and maximal after incubation of 2 h). When extracellular Na+ was replaced isosmotically with choline, N-methyl-D-glucamine, or glucose, histamine release also was observed after direct stimulation with IL-3. The effect was 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-dependently inhibited anti-IgE- and IL- 3-induced histamine release. The inhibitory effects on Na+ and K+ were slightly additive, suggesting an action via the same pathway, which most probably is membrane potential. These results indicate that: 1) IL- 3 can induce TB+ decrease without concomitant histamine release, 2) basophils from normal subjects can release histamine on challenge with IL-3 once the inhibitory effect of Na+ is removed, and 3) Na+ and K+ down-regulate IL-3 as well as anti-IgE-induced histamine release.
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