DEGRANULATION OF HUMAN BASOPHILS BY PICOMOLAR CONCENTRATIONS OF IL-3,IL-5, OR GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

In most secretory cells, an increase in the cytosolic free Ca2+ concen tration ([Ca2+](i)) is associated with the exocytosis response. In thi s study we have evaluated the effect of thapsigargin on histamine rele ase from purified (70% to 97% pure) human basophils of nonallergic don ors. Thapsigargin (2 mu mol/L), by inhibiting the uptake of Ca2+ in th e stores of the endoplasmic reticulum, leads within 1 minute to a grad ual increase in [Ca2+](i) in human basophils. Incubation of basophils with thapsigargin by itself induced only a very small release of hista mine (5.6% +/- 1.8%). However, under suboptimal conditions of stimulat ion with other agonists, preincubation of basophils with thapsigargin significantly enhanced histamine release. Most strikingly, addition of thapsigargin made basophils extremely sensitive for histamine release induced by IL-3 (maximum histamine release, 71% +/- 7%), IL-5 (maximu m histamine release, 43% +/- 8%), or granulocyte-macrophage colony-sti mulating factor (GM-CSF) (maximum histamine release, 57% +/- 10%). The se cytokines by themselves did not induce histamine release in purifie d basophils. The effect of thapsigargin was mimicked to a limited exte nt by addition of platelet-activating factor. We conclude that depleti on of the Ca2+ stores may be a critical event in the activation of rec eptor-mediated histamine release in human basophils.