Microtubule disruption suppresses allergic response through the inhibition of calcium influx in the mast cell degranulation pathway
Microtubule disruption suppresses allergic response through the inhibition of calcium influx in the mast cell degranulation pathway
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DOI：
10.4049/jimmunol.174.8.4584
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Ozaki, H
中科院分区：
文献类型：
--
作者：
Oka, T;Hori, M;Ozaki, H
肥大细胞是一种分泌细胞，释放含有炎症介质的颗粒。最近的一些数据表明，细胞骨架在这一过程中发挥作用。然而，微管在Ca（2+）信号转导中的作用尚未得到很好的定义。在这项研究中，我们表明，微管细胞骨架是重要的，以维持钙21流入肥大细胞的脱粒途径，使用微管解聚剂诺考达唑和秋水仙碱。微管解聚剂抑制银诱导的RBL-2 H3细胞和骨髓源性肥大细胞的脱颗粒。当细胞在微管解聚剂存在下用Ag刺激时，Ca 21内流减少，而不影响内质网（ER）的Ca（2+）释放。诺考达唑也能抑制内质网膜Ca（2+）-ATP酶抑制剂毒胡萝卜素和环匹阿尼酸诱导的容量性Ca（2+）内流。荧光探针分析表明，诺考达唑破坏微管的形成，改变ER的胞质分布。微管解聚剂可减轻Sprague道利大鼠背部皮肤的被动皮肤过敏反应。这些结果表明，肥大细胞中的微管细胞骨架是重要的，以维持银诱导的电容性Ca 2+内流，这是负责脱粒和过敏反应。
Mast cells are secretory cells that release their granules, which contain inflammatory mediators. Some recent data suggested that cytoskeletons play a role in this process. However, the role of microtubules in Ca (2+) signaling has not yet been well defined. In this study, we demonstrate that the microtubule cytoskeleton is important to maintain Ca 21 influx in the degranulation pathway of mast cells, using the microtubule depolymerizers nocodazole and colchicine. The microtubule depolymerizers inhibited Ag-induced degranulation in RBL-2H3 cells and bone marrow-derived mast cells. When the cells were stimulated with Ag in the presence of the microtubule depolymerizers, the Ca 21 influx was decreased without affecting Ca (2+) release from the endoplasmic reticulum (ER). Capacitative Ca (2+) entry, which was induced by inhibitors of Ca (2+)-ATPase in the ER membrane, thapsigargin and cyclopiazonic acid, was also decreased by nocodazole. Fluorescent probe analysis demonstrated that nocodazole disrupted microtubule formation and changed the cytoplasmic distribution of the ER. The microtubule depolymerizers attenuated the passive cutaneous anaphylaxis reaction in back skin of Sprague Dawley rats. These results suggest that the microtubule cytoskeleton in mast cells is important to maintain Ag-induced capacitative Ca2+ entry, which is responsible for degranulation and the allergic response.