Basophils from patients with allergic asthma show a primed phenotype

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 micromol/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).

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.

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).

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).

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.