Regulation of human basophil activation: the role of Na+ and Ca2+ in IL-3-induced potentiation of IgE-mediated histamine release from human basophils

SUMMARY The release of mediators from human basophils is strongly enhanced by lL-3. However, the signalling pathways of IL-3 arc poorly defined in these cells. Since external Ca2+ and Na+ play important regulating roles in histamine release, the possibility that these cations could be involved in the potentiation by rL-3 of the anti-IgE-induced histamine release from human basophils was considered, and it was observed that: (i) lL-3 dramatically decreased the external Ca2+ requirement for IgE-mediated histamine release. However, histamine release from IL-3-treated basophils became only partially independent of external Ca2+, since addition of EGTA in the external medium abolished the effect of IL-3; (ii) decreasing Na+ influx by lowering external Na+ concentration in isosmotic medium inhibited thepotenEiatiiigefTeLtoriL-3on IgE-mediated release; (iii) amiloride. An inhibitor of Na+/Ca2+ and Na+/H+ exchanges, and its derivative, benzamil, more specific for Na+/Ca2+ exchanges, inhibited the release potentiated by IL-3. In contrast, the amiloride derivative 5-(N, N-dimethy1)-amiloride more specific for Na+/H+ exchanges, slightly increased the IL-3-enhaneed release. Thus, the decreased requirement for external Ca2+ and the dependence on external Na + taken with the effect of the Na+/Ca2+ exchange inhibitors, suggest that Na+/Ca2+ exchanges are involved in the IL-3-indueed enhancement of IgE-mediated human basophil histamine release.