Activation of peripheral and in vivo transmigrated neutrophils in patients with stable coronary artery disease
Activation of peripheral and in vivo transmigrated neutrophils in patients with stable coronary artery disease
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DOI：
10.1016/j.atherosclerosis.2006.08.003
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发表时间：
2007-06-01
期刊：
影响因子：
5.3
通讯作者：
Lundahl, Joachim
中科院分区：
文献类型：
--
作者：
Paulsson, Josefin;Dadfar, Elham;Lundahl, Joachim
越来越多的证据支持中性粒细胞在冠状动脉疾病 (CAD) 中的作用。然而，人们对中性粒细胞在以动脉粥样硬化斑块为代表的局部炎症部位的作用知之甚少。为了深入了解这些问题，我们应用了皮肤水泡模型，该模型可以分析体内迁移的中性粒细胞。我们假设稳定型 CAD 中的慢性炎症介导中性粒细胞的启动，从而影响中性粒细胞在炎症部位的作用结果。 13 名经血管造影证实患有 CAD 的患者以及 13 名年龄和性别匹配的对照者符合进入研究的资格。研究了外周和体内迁移中性粒细胞的炎症标志物（IL-6 和 CRP）、中性粒细胞激活（IL-8 和 MMP-9/NGAL）以及功能方面（CD11b 上调和细胞内 H2O2 产生）。患者的全身 IL-8 和 MMP-9/NGAL 浓度显着增加，表明循环中性粒细胞处于激发状态。稳定型 CAD 患者体内迁移的中性粒细胞释放 MMP-9/NGAL 的倾向增加，上调 CD11b 和产生过氧化氢的能力降低。炎症部位的这些异常可能是循环中性粒细胞处于启动状态的结果，并指出了局部炎症部位的中性粒细胞可能促成 CAD 发病机制的潜在机制。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
Accumulating evidence support a role of neutrophils in coronary artery disease (CAD). However little is known about the action of neutrophils at a local inflammatory site represented by an atherosclerotic plaque. To gain insight into these issues, we applied a skin blister model that permits analyses of in vivo transmigrated neutrophils. We hypothesised that the chronic inflammation in stable CAD mediates priming of neutrophils that impacts the out-come of neutrophil action at an inflammatory site. Thirteen patients with angiographically verified CAD were eligible for study entry together with 13 age and sex matched controls. Markers of inflammation (IL-6 and CRP), neutrophil activation (IL-8 and MMP-9/NGAL), and functional aspects (CD11b up-regulation and intracellular H2O2 production) of peripheral and in vivo transmigrated neutrophils were studied. Systemic IL-8 and MMP-9/NGAL concentrations were significantly increased in patients indicating a primed state in circulating neutrophils. In vivo transmigrated neutrophils in stable CAD patients had an increased propensity to release MMP-9/NGAL and a reduced capacity to up-regulate CD11b and to produce hydrogen peroxide. These aberrations at the inflammatory site may be a consequence of a primed state of circulating neutrophils and point towards potential mechanisms whereby neutrophils at a local inflammatory site may contribute to the pathogenesis of CAD. (c) 2006 Elsevier Ireland Ltd. All rights reserved.