Basophils from patients with allergic asthma show a primed phenotype

Background: IL-3, IL-5, and GM-CSF are not able to induce histamine release in purified basophils of nonallergic donors. However, we have recently found that preincubation with 2 μmol/L thapsigargin, which induces a rise in intracellular free calcium ions, renders human basophils extremely sensitive for IL-3, IL-5, or GM-CSF, leading to enhanced histamine release. Histamine release was also induced in the reverse order (first cytokine and then thapsigargin). Objective: Because these cytokines are supposed to be increased in allergic inflammation, we examined whether basophils of patients with allergic asthma showed an enhanced response to thapsigargin. Methods: We measured the histamine release induced by thapsigargin in a group of allergic asthmatic subjects (n = 24) and compared this response with those of 3 control groups. The control groups consisted of healthy control subjects (group 1, n = 21); patients with a nonallergic, nonasthmatic lung disease (group 2, n = 22); and patients with nonallergic asthma (group 3, n = 9). Results: There was no difference in spontaneous histamine release. Also, no significant difference in histamine release was found when anti-IgE or formyl-methionyl-leucyl-phenylalanine was used as a stimulus. Histamine release induced by IL-3 alone or a combination of IL-3 and thapsigargin also did not differ. In contrast, basophils from the group with allergic asthma showed a significantly higher percentage of histamine release induced by thapsigargin (38.2% ± 13.2%) than did basophils from the 3 control groups (healthy control subjects, 22.5% ± 6.9%; subjects with lung disease, 24.9% ± 8.9%; subjects with nonallergic asthma 15.0% ± 3.0%; all mean ± SD). Conclusion: These data indicate that basophils in peripheral blood of subjects with allergic asthma have a primed phenotype and that thapsigargin- induced histamine release is a practical tool to study this phenomenon.