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循环树突状细胞前体细胞在急性心肌梗死中的募集和促炎反应。

Recruitment of circulating dendritic cell precursors into the infarcted myocardium and pro-inflammatory response in acute myocardial infarction.

机构信息

Department of Internal Medicine I, Division of Cardiology and Intensive Care Medicine, University Hospital Jena, Jena, Germany.

出版信息

Clin Sci (Lond). 2012 Sep;123(6):387-98. doi: 10.1042/CS20110561.

DOI:10.1042/CS20110561
PMID:22494099
Abstract

DC (dendritic cells) play an important role in the immune system. They invade peripheral tissues to detect harmful antigens, inducing a local immune response. Studies suggest that DCPs (dendritic cell precursors) might be reduced in AMI (acute myocardial infarction); however, the reason for their reduction is unknown yet. In the present study, circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs), tDCPs (total DCPs) and serum levels of TNFα (tumour necrosis factor α), IL (interleukin)-2, -4, -5, -6, -10 and -12 were analysed by flow cytometry in blood of patients with NSTEMI [non-STEMI (ST-segment elevation myocardial infarction)] (n=44) and STEMI (n=34) compared with controls with excluded CAD (coronary artery disease) (n=45). Post-mortem myocardial specimens of patients with AMI (n=12) and healthy myocardium of accident victims (n=10) were immunostained for mDCs (myeloid dendritic cells) T-cells and macrophages. Compared with controls, in patients with AMI a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.0001). The extent of the decrease was higher in STEMI than NSTEMI patients. Serum levels were significantly higher in patients with AMI compared with controls for IL-6, -10, -12 and TNFα (each P<0.03). Immunostaining revealed significantly higher number of DCs, T-cells and macrophages (each P<0.002) in infarcted than control myocardium. We show that circulating DCPs are significantly reduced in AMI, with a pronounced reduction in STEMI patients. This was accompanied by a significant increase of inflammatory serum cytokines in patients with AMI. Immunohistochemical analysis unravelled that the reduction of circulating DCPs might be due to recruitment into the infarcted myocardium.

摘要

树突状细胞(DC)在免疫系统中发挥重要作用。它们侵入外周组织以检测有害抗原,从而诱导局部免疫反应。研究表明,在急性心肌梗死(AMI)中,DC 前体(DCP)可能减少;然而,其减少的原因尚不清楚。本研究通过流式细胞术分析了非 ST 段抬高型心肌梗死(NSTEMI)[非 ST 段抬高型心肌梗死(ST 段抬高型心肌梗死)]患者(n=44)和 ST 段抬高型心肌梗死(STEMI)患者(n=34)与排除 CAD(冠状动脉疾病)的对照组(n=45)的血液中循环 mDCP(髓样 DCP)、pDCP(浆细胞样 DCP)、tDCP(总 DCP)以及 TNFα(肿瘤坏死因子α)、IL(白细胞介素)-2、-4、-5、-6、-10 和 -12 的血清水平。对 AMI 患者(n=12)的死后心肌标本和意外受害者的健康心肌(n=10)进行免疫染色,用于髓样树突状细胞(mDCs)、T 细胞和巨噬细胞。与对照组相比,AMI 患者的循环 mDCP、pDCP 和 tDCP 显著减少(均 P<0.0001)。STEMI 患者的减少程度高于 NSTEMI 患者。与对照组相比,AMI 患者的血清 IL-6、-10、-12 和 TNFα 水平显著升高(均 P<0.03)。免疫染色显示,梗死心肌中 DC、T 细胞和巨噬细胞的数量显著增加(均 P<0.002)。我们表明,AMI 患者的循环 DCP 明显减少,STEMI 患者的减少更为明显。这伴随着 AMI 患者的炎症血清细胞因子显著增加。免疫组织化学分析揭示,循环 DCP 的减少可能是由于其募集到梗死心肌中。

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