Särndahl Eva, Bergström Ida, Brodin Veronika Patcha, Nijm Johnny, Lundqvist Setterud Helen, Jonasson Lena
Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
PLoS One. 2007 Oct 24;2(10):e1056. doi: 10.1371/journal.pone.0001056.
During the last years, neutrophils have emerged as important players in atherogenesis. They are highly activated in peripheral blood of patients with unstable angina. Moreover, a primed state of circulating neutrophils has been proposed in patients with stable angina. Our aim was to investigate the neutrophil activation status in patients with stable coronary artery disease (CAD) at conventional drug treatment.
Thirty patients with stable CAD and 30 healthy controls were included using a paired design. The neutrophil expression of CD18 and high-affinity state of CD11b was analysed by flow cytometry before and after stimulation with chemoattractants. Also, the production of reactive oxygen species (ROS) was determined by chemiluminescence. During basal conditions, the neutrophil expression of CD18 or high-affinity state of CD11b did not differ between patients and controls. Chemoattractants (Interleukin-8 and Leukotriene B(4)) did not increase either the expression or the amount of high-affinity CD11b/CD18-integrins in CAD patients compared to controls, and had no effect on the production of ROS. On the other hand, the ROS production in response to C3bi-opsonised yeast particles and the neutrophils' inherent capacity to produce ROS were both significantly decreased in patients.
CONCLUSION/SIGNIFICANCE: We could not find any evidence that neutrophils in patients with stable CAD were primed, i.e. more prone to activation, compared to cells from healthy controls. According to our data, the circulating neutrophils in CAD patients rather showed an impaired activation status. It remains to be elucidated whether the neutrophil dysfunction in CAD is mainly a marker of chronic disease, an atherogenic factor or a consequence of the drug treatment.
在过去几年中,中性粒细胞已成为动脉粥样硬化形成过程中的重要参与者。它们在不稳定型心绞痛患者的外周血中高度活化。此外,有人提出稳定型心绞痛患者的循环中性粒细胞处于预激活状态。我们的目的是研究接受常规药物治疗的稳定型冠状动脉疾病(CAD)患者的中性粒细胞活化状态。
采用配对设计纳入了30例稳定型CAD患者和30名健康对照者。在用趋化因子刺激前后,通过流式细胞术分析中性粒细胞CD18 的表达和CD11b的高亲和力状态。此外,通过化学发光法测定活性氧(ROS)的产生。在基础条件下,患者和对照者之间中性粒细胞CD18的表达或CD11b的高亲和力状态没有差异。与对照相比,趋化因子(白细胞介素-8和白三烯B4)在CAD患者中既没有增加高亲和力CD11b/CD18整合素的表达也没有增加其数量,并且对ROS的产生没有影响。另一方面,患者对C3bi调理的酵母颗粒产生的ROS以及中性粒细胞产生ROS的固有能力均显著降低。
结论/意义:我们没有发现任何证据表明,与健康对照者的细胞相比,稳定型CAD患者的中性粒细胞处于预激活状态,即更容易被激活。根据我们的数据,CAD患者的循环中性粒细胞显示出活化状态受损。CAD中的中性粒细胞功能障碍究竟主要是慢性疾病的标志物、致动脉粥样硬化因子还是药物治疗的结果,仍有待阐明。