Major trauma enhances store-operated calcium influx in human neutrophils
Major trauma enhances store-operated calcium influx in human neutrophils
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DOI：
10.1097/00005373-200004000-00003
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发表时间：
2000-04-01
影响因子：
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通讯作者：
Deitch, EA
中科院分区：
文献类型：
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作者：
Hauser, CJ;Fekete, Z;Deitch, EA
目的：炎症部位的趋化因子通过胞内钙离子([Ca~(2+)](I))流作为第二信使激活或激活中性粒细胞(PMN)。[Ca~(2+)](I)可通过受体介导的内流或储藏释放而迅速动员，而外源钙内流(SOI)的动员则较慢。我们研究了趋化因子对[Ca~(2+)](I)的动员以及创伤对趋化物质钙内流机制的影响。比较早期和晚期[Ca~(2+)](I)电流对钙离子净通量的贡献，在较开放的激动剂(fMLP、C5a、PAF)和较弱的激动剂(IL-8、Gro-α和LTB_4)刺激后，通过[Ca~(2+)](I)外流曲线下面积与[Ca~(2+)](I)外流曲线(外流曲线)下面积的比值来反映Store操作的[Ca~(2+)](I)动员。创伤患者(ISS>；25例)和配对志愿者(n=7对)的PMN用thapsigargin启动和刺激，比较细胞钙储备和SOCI。结果：晚动员对fMLP、PAF和C5a信号的贡献大于对IL-8、Gro-α和LTB4信号的贡献(p<；0.01)。创伤后中性粒细胞的钙储备量和储存量仅略有下降(p=0.0 5)，但创伤后中性粒细胞[Ca~(2+)](I)内流明显增加(p=0.007)，净钙显著增加(p=0.034)。结论：SOI可能在中性粒细胞活化中起重要作用，创伤后中性粒细胞SOCI升高，[Ca~(2+)](I)升高可能改变趋化素类的刺激反应偶联，从而导致中性粒细胞功能障碍。
Purpose: Chemotaxins from inflammatory sites prime or activate neutrophils (PMN) by using cytosolic calcium ([Ca2+](i)) fluxes as second messengers. [Ca2+](i) can be mobilized rapidly by receptor-mediated entry or store-release, of more slowly by store-operated calcium influx (SOCI), We studied [Ca2+](i) mobilization by chemotaxins and how trauma impacts the calcium entry mechanisms used by chemotaxins.Methods: [Ca2+](i) flux was studied by spectrofluorometry. The contributions of early and late [Ca2+](i) currents to net calcium flux were compared after stimulation by more patent (fMLP, C5a, PAF) or less potent (IL-8, GRO-alpha, and LTB4) agonists, Store operated [Ca2+](i) mobilization was reflected by the ratio of area under the [Ca2+](i) efflux curve to peak [Ca2+](i) (efflux curve). PMN from trauma patients (ISS > 25) and pair-matched volunteer (n = 7 pairs) were then primed and stimulated with thapsigargin to compare cell calcium stores and SOCI.Results: Late [Ca2+](i) mobilization made more important contributions to fMLP, PAF, and C5a signals than to IL-8, GRO-alpha, or LTB4 (p < 0.01 all comparisons). Calcium stores and store release were only marginally lower after injury (p = not significant), but trauma PMN showed far higher [Ca2+](i) influx after thapsigargin (p = 0.007), and greater net SOCI (p = 0.034).Conclusions: SOCI may play an important role in PMN activation, and trauma increases PMN SOCI, Prolonged elevations of [Ca2+](i) due to enhanced SOCI may alter stimulus-response coupling to chemotaxins and contribute to PMN dysfunction after injury.