Ionic regulation of human basophil releasability. I. Inhibitory effect of copper

Abstract

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.

Expression of Actin and Tubulins in Purified Human Basophil Leukocytes upon Stimulation with IL-3

“…This is interesting because both morphological and pharmacological observations [6, 7, 9, 42]indicate that actin plays a role in the histamine release process in basophils and mast cells.…”

“…It has long been recognized that tubulins play a role in the histamine release process in basophils and mast cells. Tubulin-depolymerizing drugs like colchicine inhibit histamine release, while tubulin-stabilizing agents such as D 2 O enhance histamine release [6, 7, 9, 42, 43], indicating that polymerization of tubulin is a part of the process leading to histamine release. We found a similarity between the amount of histamine release and the amount of tubulin expression, thereby providing stoichiometric data suggesting that tubulins do play a role in basophil histamine release.…”

Ionic regulation of human basophil releasability. II. Non‐releasing basophils are converted into releasing basophils in a low‐Na+ medium

“…Tt has been recognized that Ca-^ ions play an important role in basophil activation, which is to say that they potentiate histamine release [6,7]. However, other ions, as, Sr^+, Na"*^ and Cv'^^, can interfere with histamine release [8][9][10][11][12][13].…”