Ca2+ influx‐mediated histamine synthesis and IL‐6 release in mast cells activated by monomeric IgE
Ca2+ influx‐mediated histamine synthesis and IL‐6 release in mast cells activated by monomeric IgE
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DOI：
10.1002/eji.200425622
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发表时间：
2005-02
影响因子：
5.4
通讯作者：
Satoshi Tanaka;Sonoko Mikura;Eri Hashimoto;Y. Sugimoto;A. Ichikawa
中科院分区：
文献类型：
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作者：
Satoshi Tanaka;Sonoko Mikura;Eri Hashimoto;Y. Sugimoto;A. Ichikawa
我们先前证明，在IL-3依赖性小鼠骨髓源性肥大细胞（BMMC）中，抗DNP IgE克隆SPE-7致敏后，组胺合成被显著诱导。我们发现SPE-7诱导的Ca 2+动员表现出与毒胡萝卜素诱发的容量性Ca 2+内流相似的特征。发现肥大细胞活化的潜力在不同的IgE克隆之间变化，并且单价半抗原DNP-赖氨酸抑制SPE-7诱导的活化。SPE-7诱导的Ca 2+动员被特异性钙库操纵的Ca 2+通道抑制剂SK&F 96365有效抑制，但更广谱的Ca 2+通道抑制剂La 3+和Gd 3+完全不抑制，而Ag刺激诱导的Ca 2+动员被这些抑制剂抑制。在体外分化的肥大细胞中，SPE-7也诱导了Ca 2+动员，尽管组胺合成和IL-6释放的增加小于BMMC。这些结果表明，Ca 2+内流通过与Ag刺激不同的机制操作，对于肥大细胞中组胺合成和IL-6释放的增加至关重要。
We previously demonstrated that histamine synthesis is drastically induced upon sensitization with an anti‐DNP IgE clone, SPE‐7, in IL‐3‐dependent mouse bone marrow derived mast cells (BMMC). We found that Ca2+ mobilization induced by SPE‐7 exhibited a similar profile to the capacitative Ca2+ entry evoked by thapsigargin. Potentials for activation of mast cells were found to vary between different IgE clones, and a monovalent hapten, DNP‐lysine, suppressed the activation induced by SPE‐7. Ca2+ mobilization induced by SPE‐7 was suppressed potently by the specific store‐operated Ca2+ channel inhibitor, SK&F 96365, but not at all by Ca2+ channel inhibitors with more broad spectrum, La3+ and Gd3+, whereas the Ca2+ mobilization induced by Ag stimulation was suppressed by these inhibitors. Ca2+ mobilization was also induced by SPE‐7 in in vitro differentiated mast cells, although the increases in histamine synthesis and IL‐6 release were smaller than those in BMMC. These results suggest that Ca2+ influx operated by a distinct mechanism from that in Ag stimulation is essential for increased histamine synthesis and IL‐6 release in mast cells.