Capacitative Ca2+ influx and activation of the neutrophil respiratory burst. Different regulation of plasma membrane‐ and granule‐localized NADPH‐oxidase

Capacitative Ca2+ influx and activation of the neutrophil respiratory burst. Different regulation of plasma membrane‐ and granule‐localized NADPH‐oxidase
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电容性 Ca2+ 流入和中性粒细胞呼吸爆发的激活质膜和颗粒定位 NADPH 氧化酶的不同调节。

DOI:
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发表时间:
2002
影响因子:
5.5
通讯作者:
A. Karlsson
A. Karlsson
中科院分区:
医学3区
文献类型:
--
作者:
D. Granfeldt;M. Samuelsson;A. Karlsson

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中性粒细胞 NADPH 氧化酶可能在质膜中被激活,导致氧代谢物释放到细胞外,或者在颗粒或吞噬体膜中释放,从而在细胞内产生氧化剂。通过 fMLF 与其受体结合介导的 [Ca2+]i 增加是激活质膜定位氧化酶的信号级联的一部分。相反,Ca2+ 离子载体诱导的 [Ca2+]i 升高会导致细胞内氧化酶池的激活。我们用毒胡萝卜素模拟了 fMLF 诱导的细胞内 Ca2+ 储备的排空。这诱导了明显的细胞内氧化酶活性,但没有氧化剂释放到细胞外。毒胡萝卜素诱导的效应依赖于电容性 Ca2+ 流入,因为该效应受到 EGTA 和 Ca2+ 通道阻滞剂 La3+ 剂量依赖性的抑制。当 La3+ 浓度在 200 至 400 μM 之间时,毒胡萝卜素还可诱导细胞外大量产生超氧阴离子。测试的其他通道阻滞剂没有引起类似的效果。我们得出的结论是,电容性 Ca2+ 流入导致 [Ca2+]i 升高,从而诱导细胞内位点的 NADPH 氧化酶激活。此外,质膜定位的 NADPH 氧化酶的激活受到更复杂的 Ca2+ 信号传导的调节,包括电容性 Ca2+ 流入以及可能的 La3+ 敏感 Ca2+ 通道的特异性作用。
The neutrophil NADPH‐oxidase may be activated in the plasma membrane, resulting in release of oxygen metabolites extracellularly, or in the granule or phagosomal membranes, giving intracellular production of oxidants. An increase in [Ca2+]i mediated through binding of fMLF to its receptor is part of a signaling cascade that activates the plasma membrane‐localized oxidase. In contrast, a rise in [Ca2+]i induced by a Ca2+ ionophore results in activation of the intracellular pool of oxidase. We mimicked fMLF‐induced emptying of intracellular Ca2+ stores with thapsigargin. This induced a pronounced intracellular oxidase activity but no extracellular release of oxidants. The thapsigargin‐induced effect was dependent on capacitative Ca2+ influx, because the effect was inhibited dose‐dependently by EGTA and the Ca2+ channel blocker La3+. At La3+ concentrations between 200 and 400 μM, thapsigargin also induced a massive extracellular production of superoxide anion. No other channel blockers tested induced a similar effect. We conclude that elevation in [Ca2+]i by capacitative Ca2+ influx induces NADPH‐oxidase activation at an intracellular site. Further, activation of the plasma membrane‐localized NADPH‐oxidase is regulated by a more complex Ca2+ signaling, involving capacitative Ca2+ influx and possibly the specific action of La3+‐sensitive Ca2+ channels.
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DOI: --
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