IONIC REGULATION OF HUMAN BASOPHIL RELEASABILITY .2. NON-RELEASING BASOPHILS ARE CONVERTED INTO RELEASING BASOPHILS IN A LOW-NA+ MEDIUM

The effects of different extracellular Na+ and Ca2+ concentrations on histamine release from human basophils were investigated. Isosmotic re placement of extracellular Na+ either with choline(+), a non-permeant Na+ analogue, or glucose significantly increased spontaneous and anti- IgE-induced histamine release. Basophils from 12 of 49 normal subjects , which were found not to release histamine upon challenge with an opt imal dose of anti-IgE in a 135 mM NaCl buffer, were converted into rel easing basophils when stimulation with anti-IgE was performed in a low -Naf medium. The increase in Na+ concentration in the extracellular me dium was accompanied by a reduction in the magnitude of basophil respo nse to anti-IgE, which was significantly more pronounced in non-releas ers than in releasers (per cent inhibition by 70 mM NaCl 75.5+/-3.2 v 43.5+/-9.0, P <0.01). At higher Naf concentrations a progressive and a lmost complete abrogation of histamine release was observed in non-rel easers, but not in releasers (maximal per cent inhibition at 140 mM Na Cl 97.3+/-1.3 vs 50.4+/-8.6). The Na+/H+ exchanger monensin had a dose -dependent inhibitory effect on anti-IgE-induced histamine release, an d the concentration inhibiting 50% of histamine release was 1.5 x 10(- 7) M. When basophils were challenged in the presence of different Naand Ca2+ concentrations, it was shown that the two cations have antago nistic effects, which is to say that they down-regulate and upregulate histamine release, respectively. Moreover, the requirement of extrace llular Ca2+ was lowered in a low-Na+ medium. These results suggest tha t Na+ and Ca2+ ions contribute with opposite effects to the modulation of basophil response to anti-IgE and that non-releasing basophils are converted into releasing basophils in a low-Naf medium.