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It has been demonstrated that Na+ down-regulates IgE-dependent and IgE-independent histamine release from basophils of normal subjects. The aim of this study was to evaluate whether Na+ exerts its inhibitory effect on basophil histamine release in patients with systemic sclerosis (SSc). Peripheral blood leucocytes were stimulated with anti-IgE, N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) and IL-3 in the presence of high and low Na+ concentrations, and histamine release was measured by a fluorometrie method. The dose--response curves of histamine release induced by the above stimuli were similar in SSc patients (n = 15) and in normal subjects (n = 39). Na+ removal from the extracellular medium and its isosmotic replacement with choline chloride led to a significant increase of anti-IgE- and fMLP-induced histamine release in normal subjects, but not in SSc patients. In the former population, histamine release induced by an optimal dose of anti-IgE (&frac15000;) was 26.4 ± 3.1% in high Na+ and 59.3 ± 3.5% in low Na+ (mean ± s.e.m., P < 0.0001), whereas in the latter population mean histamine release was 20.4 ± 5.1% in high Na+ and 15.8 ± 2.9% in low Na+ (P NS). A similar trend was observed when basophils were stimulated with fMLP. Na+ exerted a dose-dependent inhibitory effect on anti-IgE- and fMLP-induced histamine release in normal subjects, but not in SSc patients. IL-3-induced histamine release from basophils of SSc patients was increased in a low-Na+ solution, but to a lesser extent when compared with normal controls. Therefore basophils from normal subjects and SSc patients behave in a different way when stimulated in a low-Na+ medium. The inhibitory effect of Na+ on basophil histamine release is impaired in SSc patients, and this abnormality could contribute to basophil dysfunction. [ABSTRACT FROM AUTHOR]

The effects of different extracellular Na+ and Ca2+ concentrations on histamine release from human basophils were investigated. Isosmotic replacement 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 optimal dose of anti-IgE in a 135 mM NaCI buffer, were converted into releasing basophils when stimulation with anti-IgE was performed in a low-Na medium. The increase in Na+ concentration in the extracellular medium was accompanied by a reduction in the magnitude of basophil response to anti-IgE, which was significantly more pronounced in non-releasers than in releasers (per cent inhibition by 70 mM NaCI 75.5 ±3.2 vs 43.5 + 9.0, P<0.01). At higher Na+ concentrations a progressive and almost complete abrogation of histamine release was observed in non-releasers, but not in releasers (maximal per cent inhibition at 140 mM NaCI 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, and the concentration inhibiting 50% of histamine release was 1.5 × 10-7M. When basophils were challenged in the presence of different Na+ and Ca2+ concentrations, it was shown that the two cations have antagonistic effects, which is to say that they down-regulate and upregulate histamine release, respectively. Moreover, the requirement of extracellular Ca2+ was lowered in a low-Na+ medium. These results suggest that 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-Na+ medium. [ABSTRACT FROM AUTHOR]