Regulation of human basophil activation; the role of Na+ and Ca2+ in IL-3-induced potentiation of IgE-mediated histamine release from human basophils.
The release of mediators from human basophils is strongly enhanced by IL-3. However, the signalling pathways of IL-3 are 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 IL-3 of the anti-IgE-induced histamine release 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-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 the potentiating effect of IL-3 on 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-dimethyl)-amiloride, more specific for Na+/H+ exchanges, slightly increased the IL-3-enhanced 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-induced enhancement of IgE-mediated human basophil histamine release.
Beauvais
F
F
INSERM U200, Université Paris-Sud, Clamart, France.
Echasserieau
K
K
Burtin
C
C
Benveniste
J
J
D000584:Amiloride / Q000494:pharmacology; D001491:Basophils / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology*
D007377:Interleukin-3; D007073:Immunoglobulin E; D000584:Amiloride; D012964:Sodium; D002118:Calcium