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瓣膜手术和金黄色葡萄球菌菌血症后房室瓣中α5β1整合素、纤连蛋白、血管细胞黏附分子-1、巨噬细胞集落刺激因子-1/原癌基因c-fms和单核细胞趋化蛋白-1的转录调控

Transcriptional regulation of alpha5beta1 integrin, fibronectin, VCAM-1, MCSF-1/c-fms, and MCP-1 in atrioventricular valves after valvular surgery and Staphylococcus aureus bacteremia.

作者信息

Eichinger Walter Benno, Grammer Joachim Burkhard, Zhao Bo, Brückner Juliane, Mendler Nikolaus, Lange Rüdiger, Bauernschmitt Robert

机构信息

German Heart Center Munich at the Technical University of Munich, Department of Cardiac and Vascular Surgery, Germany.

出版信息

Cytokine. 2005 Sep 21;31(6):465-72. doi: 10.1016/j.cyto.2005.07.005.

DOI:10.1016/j.cyto.2005.07.005
PMID:16115779
Abstract

OBJECTIVE

The primary event in the development of infective endocarditis (IE) is bacterial adherence to damaged heart valves. This includes capture, adhesion and internalization of bacteria into host cells.

METHODS

We determined in an experimental rabbit model for IE whether a transient bacteremia caused by Staphylococcus aureus and/or endothelial heart valve lesions induce transcriptional regulation of alpha(5)beta(1) integrin, fibronectin, vascular cell adhesion molecule-1 (VCAM-1), macrophage colony-stimulating factor-1 (MCSF-1), c-fms proto-oncogene (MCSF-1 receptor), and macrophage chemoattractant protein-1 (MCP-1) in mitral and tricuspid valves.

RESULTS

No significant upregulation was found after isolated bacteremia. Six hours after surgical manipulation valvular endothelial lesions led to a distinct modulation in the mRNA expression of proinflammatory cytokines (MCSF-1 and MCP-1), VCAM-1 and alpha(5)beta(1) integrin. The most evident differences between the mitral and tricuspid valves were seen in the significant upregulation of VCAM-1 mRNA on the tricuspid valve in the surgical groups, whereas there was no effect on the mitral valve. MCSF-1 and MCP-1 were dramatically upregulated in both valves after surgery.

CONCLUSIONS

During the host defence mechanisms in the development of IE proinflammatory cytokines, cellular adhesion molecules, and molecules of the fibronectin/integrin axis are activated, showing distinct differences in right- and left-sided heart valves.

摘要

目的

感染性心内膜炎(IE)发展过程中的主要事件是细菌黏附于受损的心脏瓣膜。这包括细菌被宿主细胞捕获、黏附及内化。

方法

我们在IE实验兔模型中确定,由金黄色葡萄球菌引起的短暂菌血症和/或心脏瓣膜内皮损伤是否会诱导二尖瓣和三尖瓣中α(5)β(1)整合素、纤连蛋白、血管细胞黏附分子-1(VCAM-1)、巨噬细胞集落刺激因子-1(MCSF-1)、c-fms原癌基因(MCSF-1受体)和巨噬细胞趋化蛋白-1(MCP-1)的转录调控。

结果

单纯菌血症后未发现明显上调。手术操作6小时后,瓣膜内皮损伤导致促炎细胞因子(MCSF-1和MCP-1)、VCAM-1和α(5)β(1)整合素的mRNA表达出现明显调节。二尖瓣和三尖瓣之间最明显的差异在于手术组三尖瓣上VCAM-1 mRNA的显著上调,而二尖瓣则无此影响。手术后,MCSF-1和MCP-1在两个瓣膜中均显著上调。

结论

在IE发展过程中的宿主防御机制中,促炎细胞因子、细胞黏附分子以及纤连蛋白/整合素轴分子被激活,左右侧心脏瓣膜表现出明显差异。

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