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 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.
Tedeschi
A
A
Department of Internal Medicine, University of Milan, IRCCS Ospedale Policlinico, Italy.
Palella
M
M
Milazzo
N
N
Lorini
M
M
Miadonna
A
A
D015761:4-Aminopyridine / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D001491:Basophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D006096:Gramicidin / Q000009:adverse effects; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*; D012964:Sodium / Q000502:physiology*; D014048:Tolonium Chloride / Q000378:metabolism
D007377:Interleukin-3; D006096:Gramicidin; D014048:Tolonium Chloride; D012964:Sodium; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium