Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction
Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction
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DOI：
10.1160/th09-02-0103
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发表时间：
2009-09-01
影响因子：
6.7
通讯作者：
Kubicek, Markus
中科院分区：
文献类型：
--
作者：
Distelmaier, Klaus;Adlbrecht, Christopher;Kubicek, Markus
动脉粥样硬化斑块破裂以及随后的附壁血栓形成被认为是急性心肌梗死（AMI）中影响心外膜血流的主要事件。然而，急性冠状动脉闭塞的确切机制尚不清楚。我们通过二维凝胶电泳和ELISA比较了AMI患者全身血浆和血栓形成部位血浆的蛋白质组谱。我们发现了补体系统的局部激活，补体激活剂 C 反应蛋白 (CRP) 和下游补体效应器 C3a 和 C5a 的选择性积累。冠状动脉血栓中的 CRP 与 CIq 和 C3 免疫反应性共定位，表明经典的补体激活。在体外，冠状动脉血栓衍生的血浆以 C5a 依赖性方式增强中性粒细胞趋化性。在体内，血栓形成部位的中性粒细胞积聚与从症状出现到第一次球囊膨胀或抽吸的时间延迟平行，并且与 C5a 和酶促梗塞面积相关。我们提出了急性冠状动脉血栓中局部补体激活的第一个直接证据。我们的数据表明，局部补体效应器通过增强中性粒细胞募集来放大 AMI 中的血管闭塞过程。
Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main event compromising epicardial flow in acute myocardial infarction (AMI). However, the precise mechanisms underlying acute coronary occlusion are unknown.We compared the proteomic profiles of systemic plasma and plasma derived from the site of thrombus formation of patients with AMI by two-dimensional gel electrophoresis and ELISA. We identified a local activation of the complement system, with selective accumulation of the complement activator C-reactive protein (CRP) and the downstream complement effectors C3a and C5a. CRP in coronary thrombus co-localised with CIq and C3 immunoreactivities, suggesting classical complement activation. In vitro, coronary thrombus derived plasma enhanced neutrophil chemotaxis in a C5a dependent fashion. In vivo, neutrophil accumulation at the site of thrombus formation paralleled the time delay from symptom onset to first balloon inflation or aspiration, and was correlated with C5a and enzymatic infarct size. We present the first direct evidence for localised complement activation in acute coronary thrombi. Our data indicate that local complement effectors amplify the vascular occlusion process in AMI by enhanced neutrophil recruitment.