Lie W J, Mul F P, Roos D, Verhoeven A J, Knol E F
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Academic Medical Center, University of Amsterdam.
J Allergy Clin Immunol. 1998 May;101(5):683-90. doi: 10.1016/S0091-6749(98)70178-2.
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.
在大多数分泌细胞中，胞质游离钙离子浓度（[Ca2+]i）的升高与胞吐反应相关。在本研究中，我们评估了毒胡萝卜素对来自非过敏供体的纯化（纯度70%至97%）人嗜碱性粒细胞组胺释放的影响。毒胡萝卜素（2微摩尔/升）通过抑制内质网储存库中钙离子的摄取，在1分钟内导致人嗜碱性粒细胞中[Ca2+]i逐渐升高。单独用毒胡萝卜素孵育人嗜碱性粒细胞仅诱导出非常少量的组胺释放（5.6%±1.8%）。然而，在与其他激动剂进行次优刺激的条件下，但毒胡萝卜素预孵育人嗜碱性粒细胞可显著增强组胺释放。最引人注目的是，添加毒胡萝卜素使人嗜碱性粒细胞对白细胞介素-3（最大组胺释放量，71%±7%）、白细胞介素-5（最大组胺释放量，43%±8%）或粒细胞-巨噬细胞集落刺激因子（GM-CSF）（最大组胺释放量，57%±10%）诱导的组胺释放极其敏感。这些细胞因子本身在纯化的嗜碱性粒细胞中不会诱导组胺释放。添加血小板活化因子在一定程度上模拟了毒胡萝卜素的作用。我们得出结论，钙离子储存库的耗竭可能是人类嗜碱性粒细胞中受体介导的组胺释放激活过程中的一个关键事件。
