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, He have recently fou nd that preincubation Kith 2 mu mol/L thapsigargin, which induces a rise in intracellular free calcium ions, renders human basophils extremely sensiti ve for IL-3, 1L-5, or GM-CSF, leading to enhanced histamine release. Histam ine 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 asth ma showed an enhanced response to thapsigargin. Methods: We measured the histamine release induced by thapsigargin in a gro up 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 nas found when anti-IgE or for myl-methionyl-leucyl-phenylalanine was used as a stimulus, Histamine releas e 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 show ed a significantly higher percentage of histamine release induced by thapsi gargin (38.2% +/- 13.2%) than did basophils from the 3 control groups (heal thy control subjects, 22.5% +/- 6.9%; subjects Kith Lung disease, 24.9% +/- 8.9%;subjects dth nonallergic asthma 15.0% +/- 3.0%; all mean +/- SD). Conclusion: These data indicate that basophils in peripheral blood of subje cts dth allergic asthma have a primed phenotype and that thapsigargin-induc ed histamine release is a practical tool to study this phenomenon.