Impaired neutrophil store-mediated calcium entry in Type 2 diabetes
Impaired neutrophil store-mediated calcium entry in Type 2 diabetes
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DOI：
10.1111/j.1365-2362.2004.01291.x
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发表时间：
2004-01-01
影响因子：
5.5
通讯作者：
Thomas, TH
中科院分区：
文献类型：
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作者：
Advani, A;Marshall, SM;Thomas, TH
背景：2型糖尿病中性粒细胞功能受损导致细菌感染和心血管疾病增加。许多中性粒细胞的功能依赖于钙信号，这涉及钙从细胞内储存的释放，随后通过细胞骨架将储存的钙转运到质膜，导致储存介导的钙进入（SMCE）进入细胞。我们假设在2型糖尿病患者中，SMCE可能存在缺陷。材料与方法采集2型糖尿病患者（DM, n = 15）和对照组（NC, n = 15）的中性粒细胞。在静息细胞和fMLP和thapsigarin刺激钙释放后，用Fura-2测定游离胞质钙[Ca2+](i)。结果患者中性粒细胞基线[Ca2+](i)高于对照组（NC 65 +/- 5 nM, DM 80 +/- 4 nM, P < 0.05）。然而，fmlp治疗后患者的[Ca2+](i)明显降低（NC 301 +/- 28 nM, DM 210 +/- 20 nM, P < 0.01）。在细胞外钙缺乏的情况下，用fMLP处理细胞时，对照组未观察到更大的增加（-倍增加，NC 2.9 +/- 0.5, DM 2.7 +/- 0.3）。用thapsigargin处理细胞引起的[Ca2+](i)的增加在对照组中比在没有细胞外钙的情况下更大（Ca2+ NC增加5.2 +/- 1.0,DM 3.0 +/- 0.4, P < 0.05； Ca2+ NC增加2.5 +/- 0.4,DM 2.2 +/- 0.2）。结论：2型糖尿病中存在中性粒细胞钙信号缺陷，通过质膜的内流受损导致游离胞质钙增加较少。异常钙信号可能在糖尿病并发症的发病机制中起重要作用。
Background In Type 2 diabetes impaired neutrophil function leads to increased bacterial infection and cardiovascular disease. Many neutrophil functions depend on calcium signalling, which involves release of calcium from intracellular stores and subsequently translocation of stores via the cytoskeleton to the plasma membrane, causing store-mediated calcium entry (SMCE) into the cell. We hypothesized that in Type 2 diabetes there would be a defect in SMCE.Materials and methods Neutrophils were prepared from patients with Type 2 diabetes (DM, n = 15) and controls (NC, n = 15). Free cytosolic calcium [Ca2+](i) was measured with Fura-2 in resting cells and after stimulation of calcium release with fMLP and thapsigargin.Results Baseline [Ca2+](i) was higher in neutrophils from the patients than the controls (NC 65 +/- 5 nM, DM 80 +/- 4 nM, P < 0.05). However, after fMLP-treatment [Ca2+](i) was significantly lower in the patients (NC 301 +/- 28 nM, DM 210 +/- 20 nM, P < 0.01). The greater increase in controls was not observed when cells were treated with fMLP in the absence of extracellular calcium (- fold increase NC 2.9 +/- 0.5, DM 2.7 +/- 0.3). Treatment of cells with thapsigargin caused a similar greater increase in [Ca2+](i) in the controls than in the patients that was not seen in the absence of extracellular calcium (- fold increase with Ca2+ NC 5.2 +/- 1.0, DM 3.0 +/- 0.4, P < 0.05; fold increase without Ca2+ NC 2.5 +/- 0.4, DM 2.2 +/- 0.2).Conclusions In Type 2 diabetes there is a defect in neutrophil calcium signalling which results in a lesser increase in free cytosolic calcium owing to impaired influx across the plasma membrane. Abnormal calcium signalling is likely to be important in the pathogenesis of diabetic complications.