REGULATION OF HUMAN BASOPHIL ACTIVATION - THE ROLE OF NA-3-INDUCED POTENTIATION OF IGE-MEDIATED HISTAMINE-RELEASE FROM HUMAN BASOPHILS( ANDCA2+ IN IL)

The release of mediators from human basophils is strongly enhanced by IL-3. However, the signalling pathways of IL-3 are poorly defined in t hese cells. Since external Ca2+ and Na+ play important regulating role s in histamine release, the possibility that these cations could be in volved in the potentiation by IL-3 of the anti-IgE-induced histamine r elease from human basophils was considered, and it was observed that: (i) IL-3 dramatically decreased the external Ca2+ requirement for IgE- mediated histamine release. However, histamine release from IL-3-treat ed 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 the potentiating effect of IL-3 on IgE-medi ated release; (iii) amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exc hanges, and its derivative, benzamil, more specific for Na+/Ca2+ excha nges, inhibited the release potentiated by IL-3. In contrast, the amil oride derivative 5-(N, N-dimethyl)-amiloride, more specific for Na+/H exchanges, slightly increased the IL-3-enhanced release. Thus, the de creased requirement for external Ca2+ and the dependence on external N a+, taken with the effect of the Na+/Ca2+ exchange inhibitors, suggest that Na+/Ca2+ exchanges are involved in the IL-3-induced enhancement of IgE-mediated human basophil histamine-release.