Ionic regulation of human basophil releasability. I. Inhibitory effect of copper.
The effects of copper (CuSO4 and CuCl2) on in vitro histamine release from human basophils stimulated by anti-IgE and Ca2+ ionophore A23187 were evaluated. Both CuSO4 and CuCl2 caused a dose-related inhibition of histamine release, which was more pronounced on anti-IgE- than on Ca2+ ionophore-induced histamine release. The concentration which produced 50% inhibition of anti-IgE-induced histamine release was 1.3 microM for CuSO4 and 1.5 microM for CuCl2; the maximal inhibition of Ca2+ ionophore-induced histamine release was 33% for CuCl2 (4 microM) and 51% for CuSO4 (16 microM). The inhibitory effect on anti-IgE-induced histamine release persisted also when extracellular Cu2+ was removed by cell washing before stimulation, whereas no inhibition of Ca2+ ionophore-induced histamine release was found when extracellular Cu2+ was removed. The activity of Cu2+ was independent of any effects of deuterium oxide and colchicine, two agents known to interact with microtubules. Increased extracellular Ca2+ concentrations reduced the inhibitory effect of CuCl2 on Ca2+ ionophore-induced histamine release, and Schild plot analysis demonstrated that Cu2+ ions are competitive antagonists of Ca2+ ions. These results indicate that Cu2+ ions in the micromolar range down-regulate anti-IgE- and Ca2+ ionophore-induced histamine release. Since Cu2+ concentration in human plasma is in the micromolar range (30 microM with 10-30% of free Cu2+), it is conceivable that Cu2+ ions contribute to the in vivo regulation of histamine release from human basophils.
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors; D003300:Copper / Q000494:pharmacology*; D019327:Copper Sulfate; D006636:Histamine Release / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D066298:In Vitro Techniques
D000888:Antibodies, Anti-Idiotypic; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D000001:Calcimycin; D003300:Copper; C028419:cuprous chloride; D019327:Copper Sulfate; D002118:Calcium