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+ concentration ([Ca2+]i) is associated with the exocytosis response. In this study we have evaluated the effect of thapsigargin on histamine release from purified (70% to 97% pure) human basophils of nonallergic donors. Thapsigargin (2 micromol/L), by inhibiting the uptake of Ca2+ in the stores of the endoplasmic reticulum, leads within 1 minute to a gradual increase in [Ca2+]i in human basophils. Incubation of basophils with thapsigargin by itself induced only a very small release of histamine (5.6% +/- 1.8%). However, under suboptimal conditions of stimulation 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 (maximum histamine release, 43% +/- 8%), or granulocyte-macrophage colony-stimulating factor (GM-CSF) (maximum histamine release, 57% +/- 10%). These cytokines by themselves did not induce histamine release in purified basophils. The effect of thapsigargin was mimicked to a limited extent by addition of platelet-activating factor. We conclude that depletion of the Ca2+ stores may be a critical event in the activation of receptor-mediated histamine release in human basophils.
Lie
W J
WJ
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Academic Medical Center, University of Amsterdam.
Mul
F P
FP
Roos
D
D
Verhoeven
A J
AJ
Knol
E F
EF
D015549:Basophil Degranulation Test; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006636:Histamine Release; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007377:Interleukin-3; D015848:Interleukin-5; D010972:Platelet Activating Factor; D019284:Thapsigargin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002118:Calcium