Cholesterol-modulating agents selectively inhibit calcium influx induced by chemoattractants in human neutrophils
Cholesterol-modulating agents selectively inhibit calcium influx induced by chemoattractants in human neutrophils
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DOI：
10.1074/jbc.m112149200
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发表时间：
2002-04-19
影响因子：
4.8
通讯作者：
Naccache, PH
中科院分区：
文献类型：
--
作者：
Barabé, F;Paré, G;Naccache, PH
测试了胆固醇干扰剂对趋化因子刺激人中性粒细胞时诱导的钙动员的影响。甲基-β-环糊精和菲律宾素不会改变钙动员的初始峰值，但会缩短添加 fMet-Leu-Phe 后钙峰值的持续时间。这些药物还抑制 fMet-Leu-Phe 或毒胡萝卜素诱导的 Mn2+ 流入。甲基-β-环糊精和菲律宾素完全消除了10（-10）m血小板激活因子诱导的钙动员，该浓度在很大程度上取决于钙的内流以及10（-7）m血小板激活因子诱导的钙内流。另一方面，甲基-β-环糊精和菲律宾素增强了由FcgammaRIIA连接诱导的钙动员，FcgammaRIIA是一种激动剂，不会诱导可检测到的钙流入。最后，甲基-β-环糊精和菲律宾素增强了对酪氨酸磷酸化谱的刺激、磷脂酶 D (PLD) 的活性以及 fMet-Leu-Phe 诱导的超氧阴离子的产生。这些结果表明，人类中性粒细胞中趋化因子利用的钙通道要么位于质膜富含胆固醇的区域，要么导致其开放的机制取决于这些微域的完整性。
The effects of cholesterol-perturbing agents on the mobilization of calcium induced upon the stimulation of human neutrophils by chemotactic factors were tested. Methyl-beta-cyclodextrin and filipin did not alter the initial peak of calcium mobilization but shortened the duration of the calcium spike that followed the addition of fMet-Leu-Phe. These agents also inhibited the influx of Mn2+ induced by fMet-Leu-Phe or thapsigargin. Methyl-beta-cyclodextrin and filipin completely abrogated the mobilization of calcium induced by 10(-10) m platelet-activating factor, which at this concentration depends to a major extent on an influx of calcium as well as the influx of calcium induced by 10(-7) m platelet-activating factor. On the other hand, methyl-beta-cyclodextrin and filipin enhanced the mobilization of calcium induced by ligation of FcgammaRIIA, an agonist that did not induce a detectable influx of calcium. Finally, methyl-beta-cyclodextrin and filipin enhanced the stimulation of the profile of tyrosine phosphorylation, the activity of phospholipase D (PLD), and the production of superoxide anions induced by fMet-Leu-Phe. These results suggest that the calcium channels utilized by chemotactic factors in human neutrophils are either located in cholesterol-rich regions of the plasma membrane, or that the mechanisms that lead to their opening depend on the integrity of these microdomains.