恶性脑肿瘤缺失基因1在细菌性心内膜炎中上调并与赘生物成分结合。

Deleted in Malignant Brain Tumors 1 is up-regulated in bacterial endocarditis and binds to components of vegetations.

作者信息

Müller Hanna, Renner Marcus, Helmke Burkhard M, End Caroline, Weiss Christel, Poeschl Johannes, Mollenhauer Jan

机构信息

Division of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.

出版信息

J Thorac Cardiovasc Surg. 2009 Sep;138(3):725-32. doi: 10.1016/j.jtcvs.2009.05.021. Epub 2009 Jul 1.

DOI:10.1016/j.jtcvs.2009.05.021

PMID:19698862

Abstract

OBJECTIVE

Bacterial endocarditis is a frequent infectious cardiac disease, especially in patients with congenital or acquired heart defects. It is characterized by bacterial colonization of the heart valves and the appearance of vegetations consisting of fibrin, blood cells, and bacteria. The glycoprotein Deleted in Malignant Brain Tumors 1 is a scavenger receptor cysteine-rich protein with functions in innate immunity and epithelial differentiation. Because of the aggregating capacity of Deleted in Malignant Brain Tumors 1, we hypothesized that an up-regulation in bacterial endocarditis may be linked to the development of vegetations.

METHODS

Heart tissue of 19 patients with bacterial endocarditis and 10 controls without bacterial endocarditis was analyzed by immunohistochemistry. The effect of human recombinant Deleted in Malignant Brain Tumors 1 on erythrocyte aggregation was measured using an automated red blood cell aggregometer MA1. Binding of human recombinant Deleted in Malignant Brain Tumors 1 to erythrocyte membranes, platelets, fibrin, and fibrinogen was analyzed by Western blotting and enzyme-linked immunosorbent assay.

RESULTS

Deleted in Malignant Brain Tumors 1 expression was up-regulated in affected heart valves with bacterial endocarditis and limited to the colonizing bacteria on the heart valves and granulocyte-depleted fibrin/fibrinogen formations, and around localized atheromatosis. Patients with aggressive bacteria showed higher DMBT1 levels than patients with less aggressive bacteria. Human recombinant Deleted in Malignant Brain Tumors 1 aggregates erythrocytes and binds to erythrocyte membranes, platelets, and fibrin/fibrinogen.

CONCLUSION

Deleted in Malignant Brain Tumors 1 up-regulation at sites of bacterial endocarditis, its association with platelets and fibrin/fibrinogen, and its ability to aggregate erythrocytes through binding to their membranes indicate a potential role in the development of vegetations and thrombosis.

摘要

目的

细菌性心内膜炎是一种常见的感染性心脏病，尤其是在先天性或后天性心脏缺陷患者中。其特征是心脏瓣膜上的细菌定植以及由纤维蛋白、血细胞和细菌组成的赘生物的出现。恶性脑肿瘤缺失基因1（Deleted in Malignant Brain Tumors 1, DMBT1）是一种富含半胱氨酸的清道夫受体蛋白，在先天免疫和上皮分化中发挥作用。由于DMBT1具有聚集能力，我们推测其在细菌性心内膜炎中的上调可能与赘生物的形成有关。

方法

采用免疫组织化学方法分析19例细菌性心内膜炎患者和10例无细菌性心内膜炎对照者的心脏组织。使用自动红细胞聚集仪MA1测定重组人DMBT1对红细胞聚集的影响。通过蛋白质印迹法和酶联免疫吸附测定法分析重组人DMBT1与红细胞膜、血小板、纤维蛋白和纤维蛋白原的结合情况。

结果

在患有细菌性心内膜炎的受影响心脏瓣膜中，DMBT1表达上调，且仅限于心脏瓣膜上的定植细菌、粒细胞减少的纤维蛋白/纤维蛋白原形成物以及局部动脉粥样硬化周围。侵袭性较强细菌感染的患者比侵袭性较弱细菌感染的患者DMBT1水平更高。重组人DMBT1可使红细胞聚集，并与红细胞膜、血小板以及纤维蛋白/纤维蛋白原结合。